Computer-Assisted Image Analysis in Assessment of Peripheral Joint MRI in Inflammatory Arthritis: A Systematic Review and Meta-analysis

Objective: To summarize the feasibility of computer-assisted quantification of joint pathologies on magnetic resonance imaging (MRI) in patients with inflammatory arthritis by evaluating the published data on reliability, validity, and feasibility. Methods: A systematic literature search was performed for original articles published from January 1, 1985, to January 1, 2021. We selected studies in which patients with inflammatory arthritis were enrolled, and arthritis-related structural damage/synovitis in peripheral joints was assessed on non-contrast-enhanced, contrast-enhanced (CE), or dynamic CE (DCE)-MRI using (semi)automated methods. Data were pooled using random-effects model. Results: Twenty-eight studies consisting of 1342 MRIs were included (mean age, 54.8 years; 66.7% female; duration of arthritis, 3.6 years). Among clinical/laboratory factors, synovial membrane volume (SV) was moderately correlated with erthrocyte sedimentation rate (ESR) level (P 0.05). Computer-aided measurement of BEV (r = 0.92), SV (r = 0.82), and DCE-MRI biomarkers (r = 0.72 N-total; r = 0.74 N-plateau; r = 0.64 N-washout) were significantly correlated with the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS; P < 0.01), allowing for earlier assessment of drug efficacy. On average, (semi)automated analysis of BEV/SV took 17 minutes (vs. 9 minutes for the RAMRIS) and DCE-MRI took 4 minutes (vs. 33 minutes for manual assessment). Conclusion: Computer-aided image quantification technologies demonstrate excellent reliability and validity when used to quantify MRI pathologies of peripheral joints in patients with inflammatory arthritis. Computer-aided evaluation of inflammatory arthritis is an emerging field and should be considered as a viable complement to conventional observer-based scoring methods for clinical trials application

Taxing the Informal Economy: The Current State of Knowledge and Agendas for Future Research

This paper reviews the literature on taxation of the informal economy, taking stock of key debates and drawing attention to recent innovations. Conventionally, the debate on whether to tax has frequently focused on the limited revenue potential, high cost of collection, and potentially adverse impact on small firms. Recent arguments have increasingly emphasised the more indirect benefits of informal taxation in relation to economic growth, broader tax compliance, and governance. More research is needed, we argue, into the relevant costs and benefits for all, including quasi-voluntary compliance, political and administrative incentives for reform, and citizen-state bargaining over taxation

Imaging assessment of children presenting with suspected or known juvenile idiopathic arthritis : ESSR-ESPR points to consider

Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease. It represents a group of heterogenous inflammatory disorders with unknown origin and is a diagnosis of exclusion in which imaging plays an important role. JIA is defined as arthritis of one or more joints that begins before the age of 16 years, persists for more than 6 weeks and is of unknown aetiology and pathophysiology. The clinical goal is early suppression of inflammation to prevent irreversible joint damage which has shifted the emphasis from detecting established joint damage to proactively detecting inflammatory change. This drives the need for imaging techniques that are more sensitive than conventional radiography in the evaluation of inflammatory processes as well as early osteochondral change. Physical examination has limited reliability, even if performed by an experienced clinician, emphasising the importance of imaging to aid in clinical decision-making. On behalf of the European Society of Musculoskeletal Radiology (ESSR) arthritis subcommittee and the European Society of Paediatric Radiology (ESPR) musculoskeletal imaging taskforce, based on literature review and/or expert opinion, we discuss paediatric-specific imaging characteristics of the most commonly involved, in literature best documented and clinically important joints in JIA, namely the temporomandibular joints (TMJs), spine, sacroiliac (SI) joints, wrists, hips and knees, followed by a clinically applicable point to consider for each joint. We will also touch upon controversies in the current literature that remain to be resolved with ongoing research

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Donors, Aid and Taxation in Developing Countries: An Overview

Recent years have witnessed rapidly growing donor interest in tax issues in the developing world. This reflects a concern with revenue collection to finance public spending, but also recognition of the centrality of taxation to growth, redistribution and broader state-building and governance goals. Against this backdrop, this paper identifies a series of key issues that demand attention if donors are to improve the quality of their support for tax reform. The focus is not, primarily, on the technical design of tax interventions, but, instead, on seven ‘big picture’ considerations for the design of donor programmes: (a) supporting local leadership of reform efforts; (b) incorporating more systematic political economy analysis into the design and implementation of reform programmes; (c) designing tax reform programmes that seek to foster broader linkages between taxation, state-building and governance; (d) paying careful attention to the complexity of the relationship between aid and tax effort; (e) better designing tax-related conditionality, particularly by developing a more nuanced set of performance indicators; (f) ensuring the effective coordination of donor interventions; and (g) paying greater attention to the international policy context, and particularly the role of tax exemptions for donor projects, tax havens and tax evasion by multinational corporations (MNCs) in undermining developing country tax systems.DfI

The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication

The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection

Looking through the 'window of opportunity': is there a new paradigm of podiatry care on the horizon in early rheumatoid arthritis?

Over the past decade there have been significant advances in the clinical understanding and care of rheumatoid arthritis (RA). Major paradigm changes include earlier disease detection and introduction of therapy, and 'tight control' of follow-up driven by regular measurement of disease activity parameters. The advent of tumour necrosis factor (TNF) inhibitors and other biologic therapies have further revolutionised care. Low disease state and remission with prevention of joint damage and irreversible disability are achievable therapeutic goals. Consequently new opportunities exist for all health professionals to contribute towards these advances. For podiatrists relevant issues range from greater awareness of current concepts including early referral guidelines through to the application of specialist skills to manage localised, residual disease activity and associated functional impairments. Here we describe a new paradigm of podiatry care in early RA. This is driven by current evidence that indicates that even in low disease activity states destruction of foot joints may be progressive and associated with accumulating disability. The paradigm parallels the medical model comprising early detection, targeted therapy, a new concept of tight control of foot arthritis, and disease monitoring