Physical activity, sedentary behaviour, and health outcomes in Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterised by high-grade local and systemic inflammation. People with RA experience a multitude of symptoms, such as chronic pain, fatigue, poor mental health and psychological wellbeing and disability, which impact their overall quality of life. People with RA typically engage in low levels of physical activity (PA) and spend long periods of time in sedentary behaviours (SB). Research suggests that increasing PA and reducing SB may improve outcomes in RA. However, this research is limited by the use of non-validated or reliable measurement methods of PA, SB, and health outcomes. In addition, studies rarely assess the different dimensions and elements of PA and SB, and their relative and independent relationships with health in people with RA. The overarching aim of this research was therefore to develop the understanding of the role of PA and SB for health in RA, through building on existing research in this domain. Specifically, the aim of this thesis was to contribute novel data examining the links between different dimensions of PA and SB with RA outcomes considered to be important by both patients and health professionals. Initiatives such as Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT), have created core outcome sets of patient- and clinician-important symptoms experienced by people with RA. This thesis focuses on the links between PA and SB with the following OMERACT outcomes: pain, disease activity, functional ability, fatigue, depression, anxiety, subjective vitality, and quality of life. First, the quality of the current evidence regarding lifestyle PA and SB interventions in people with RA was explored in a systematic review and meta-analysis (Chapter 2). In subsequent methodological chapters (Chapters 3 and 4), the reliability and validity of quantitative sensory testing (QST) modalities and reliability of different ActiGraph accelerometer model and placement site specific cut-points were investigated. The results of these methodological chapters were to inform the design and methods of a longitudinal study, to be conducted as Chapter 5 of this thesis. The aim of this study was to explore the relationships between ActiGraph-measured PA and activPAL™-measured SB with OMERACT health outcomes in people with RA. However, due to the COVID-19 pandemic, the study to be conducted as part of Chapter 5 was unable to proceed. As a consequence, Chapter 6 comprised an online survey investigating the cross-sectional associations between different dimensions of self-reported of PA and SB with OMERACT health outcomes in people with RA during the COVID-19 pandemic. Overall, thesis findings demonstrated individual links exist between lifestyle PA, non-exercise light intensity PA (LPA), walking, exercise, and sedentary time with core OMERACT patient- and clinician-important outcomes. More specifically, existing lifestyle PA and SB interventions are effective at increasing PA, reducing SB, and improving OMERACT outcomes in people with RA. Furthermore, methodological chapters suggested that QST, the ActiGraph GT9X and activPAL™ are reliable and valid assessments of pain, free-living PA, and SB, respectively. In addition, thesis findings also reported that non-exercise LPA, and walking in particular, demonstrated significant positive associations with OMERACT indicators of mental health and psychological wellbeing during the COVID-19 pandemic. These dimensions of PA should therefore be recommended to people with RA to improve mental health and psychological wellbeing, particularly during future pandemics. To conclude, this thesis provides novel evidence regarding the complex and distinct relationships between different dimensions and elements of PA and SB with core OMERACT health outcomes in people with RA, particularly during the unique worldwide event of the COVID-19 pandemic

In-flight positional and energy use data set of a DJI Matrice 100 quadcopter for small package delivery

We autonomously direct a small quadcopter package delivery Uncrewed Aerial Vehicle (UAV) or "drone" to take off, fly a specified route, and land for a total of 209 flights while varying a set of operational parameters. The vehicle was equipped with onboard sensors, including GPS, IMU, voltage and current sensors, and an ultrasonic anemometer, to collect high-resolution data on the inertial states, wind speed, and power consumption. Operational parameters, such as commanded ground speed, payload, and cruise altitude, are varied for each flight. This large data set has a total flight time of 10 hours and 45 minutes and was collected from April to October of 2019 covering a total distance of approximately 65 kilometers. The data collected were validated by comparing flights with similar operational parameters. We believe these data will be of great interest to the research and industrial communities, who can use the data to improve UAV designs, safety, and energy efficiency, as well as advance the physical understanding of in-flight operations for package delivery drones.Comment: 13 pages, 11 figures, submitted to Scientific Dat

The GstLAL Search Analysis Methods for Compact Binary Mergers in Advanced LIGO's Second and Advanced Virgo's First Observing Runs

After their successful first observing run (September 12, 2015 - January 12, 2016), the Advanced LIGO detectors were upgraded to increase their sensitivity for the second observing run (November 30, 2016 - August 26, 2017). The Advanced Virgo detector joined the second observing run on August 1, 2017. We discuss the updates that happened during this period in the GstLAL-based inspiral pipeline, which is used to detect gravitational waves from the coalescence of compact binaries both in low latency and an offline configuration. These updates include deployment of a zero-latency whitening filter to reduce the over-all latency of the pipeline by up to 32 seconds, incorporation of the Virgo data stream in the analysis, introduction of a single-detector search to analyze data from the periods when only one of the detectors is running, addition of new parameters to the likelihood ratio ranking statistic, increase in the parameter space of the search, and introduction of a template mass-dependent glitch-excision thresholding method.Comment: 12 pages, 7 figures, to be submitted to Phys. Rev. D, comments welcom

Mental health and psychological wellbeing in rheumatoid arthritis during COVID-19 - can physical activity help?

© 2020 The Authors. Published by the Mediterranean Journal of Rheumatology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://mjrheum.org/assets/files/792/file249_1200.pdfIn response to the COVID-19 pandemic, many countries have adopted community containment to manage COVID-19. These measures to reduce human contact, such as social distancing, are deemed necessary to contain the spread of the virus and protect those at increased risk of developing complications following infection with COVID-19. People with rheumatoid arthritis (RA) are advised to adhere to even more stringent restrictions compared to the general population, and avoid any social contact with people outside their household. This social isolation combined with the anxiety and stress associated with the pandemic, is likely to particularly have an impact on mental health and psychological wellbeing in people with RA. Increasing physical activity and reducing sedentary behaviour can improve mental health and psychological wellbeing in RA. However, COVID-19 restrictions make it more difficult for people with RA to be physically active and facilitate a more sedentary lifestyle. Therefore, guidance is necessary for people with RA to adopt a healthy lifestyle within the constraints of COVID-19 restrictions to support their mental health and psychological wellbeing during and after the COVID-19 pandemic

Different types of physical activity are positively associated with indicators of mental health and psychological wellbeing in rheumatoid arthritis during COVID-19

© 2020 The Authors. Published by Springer Nature. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1007/s00296-020-04751-wNationwide lockdowns during SARS-CoV-2 (COVID-19) can compromise mental health and psychological wellbeing and limit opportunities for physical activity (PA), particularly in clinical populations, such as people with rheumatoid arthritis (RA), who are considered at risk for COVID-19 complications. This study aimed to investigate associations between PA and sedentary time (ST) with indicators of mental health and wellbeing in RA during COVID-19 lockdown, and examine the moderation effects of self-isolating. 345 RA patients completed an online questionnaire measuring PA (NIH-AARP Diet and Health Study Questionnaire), ST (International Physical Activity Questionnaire-Short Form), pain (McGill Pain Questionnaire and Visual Analogue Scale), fatigue (Multidimensional Fatigue Inventory), depressive and anxious symptoms (Hospital Anxiety and Depression Scale), and vitality (Subjective Vitality Scale) during the United Kingdom COVID-19 lockdown. Associations between PA and ST with mental health and wellbeing were examined using hierarchical multiple linear regressions. Light PA (LPA) was significantly negatively associated with mental fatigue (β = − .11), depressive symptoms (β = − .14), and positively with vitality (β = .13). Walking was negatively related to physical fatigue (β = − .11) and depressive symptoms (β = − .12) and positively with vitality (β = .15). Exercise was negatively associated with physical (β = − .19) and general (β = − .12) fatigue and depressive symptoms (β = − .09). ST was positively associated with physical fatigue (β = .19). Moderation analyses showed that LPA was related to lower mental fatigue and better vitality in people not self-isolating, and walking with lower physical fatigue in people self-isolating. These findings show the importance of encouraging PA for people with RA during a lockdown period for mental health and wellbeing.This work was completed as part of a PhD studentship supported by the Medical Research Council (MRC)-Versus Arthritis Centre for Musculoskeletal Ageing Research (CMAR) (grant number: MR/K00414X/1)

The interrater and test–retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis

Introduction: Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions.Objectives: We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test–retest reliability.Methods: The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test–retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups.Results: High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01–0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP.Conclusion: PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation

Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse

Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study3, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC

World Addiction Medicine Reports : formation of the International Society of Addiction Medicine (ISAM) Global Expert Network (ISAM-GEN) and Its global surveys

Funding: All the infrastructure funding of this initiative is supported by the International Society of Addiction Medicine (ISAM). We will be open to fundraising for specific projects within the platform and future collaboration with external partners.Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.Peer reviewe

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology