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Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM.
A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review.
Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites.
Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.
Unimensional accounts of revisionism – those that align states along a single continuum from supporting the status quo to seeking a complete overhaul of the international system – miss important variation between a desire to alter the balance of military power and a desire to alter other elements of international order. We propose a two-dimensional property space that generates four ideal types: status-quo actors, who are satisfied with both order and the distribution of power; reformist actors, who are fine with the current distribution of power but seek to change elements of order; positionalist actors, who see no reason to alter the international order but do aim to shift the distribution of power; and revolutionary actors, who want to overturn both international order and the distribution of capabilities. This framework helps make sense of a number of important debates about hegemony and international order, such as the possibility of revisionist hegemonic powers, controversies over the concept of ‘soft balancing’, and broader dynamics of international goods substitution during power transitions.
The importance of concerns about status in world politics has rarely been as evident as it is today. Yet our understanding of how status dynamics influence politics and foreign policy remains limited. Dominant approaches draw on insights from social psychology about individual attitudes and behavior, but scale these up to build accounts of states as unitary or anthropomorphic actors. This results in serious theoretical problems and analytical blind spots. In this article, I offer a new framework – still rooted in social psychological insights about intergroup status dynamics – that addresses these problems. I recast the fundamental question from one about how states react to status dissatisfaction to one about how individuals – with different psychological profiles, different interests, and different positions within the national community – react to anxiety about the status of the state with they identify. I develop four broad logics that inform responses to national status dissatisfaction: identification change, emulation, transformation, and rejection. These logics subsume familiar arguments about how states seek status, but they also accommodate additional variation and explanatory possibilities. They thus constitute a more flexible framework that is better suited than existing alternatives to understand the full variety of ways in which status dynamics may influence world politics.
Tumor profiling tests can help to identify whether women with breast cancer need chemotherapy due to their risk of relapse, and some may be able to predict benefit from chemotherapy. We focused on four genetic tests: Oncotype DX (O-DX), MammaPrint (MMP), EndoPredict and Prosigna, and one immunohistochemistry test, IHC4, for the National Institute of Health and Care Excellence as part of their Diagnostic Appraisal Programme.
A systematic review was undertaken, including searching of nine databases in February 2017 plus other sources including a previous review published in 2013. The review included studies assessing clinical effectiveness of the five tumor profiling tests, with or without clinicopathological factors, to guide decisions about adjuvant chemotherapy in people with ER-positive, HER-2 negative, Stage I-II cancer with 0 to 3 positive lymph nodes (LN). The PROBAST tool and Cochrane risk of bias tools were used to assess risk of bias.
A total of 153 studies were included; the strength of evidence base for individual tests was varied. Results suggest all tests are prognostic for risk of relapse, though results were more varied in LN positive (+) patients than in LN negative (0) patients. Evidence was limited about whether tests can predict benefit from chemotherapy (available for MMP and O-DX only). Studies that assessed the impact of the tests on clinical decisions indicate that the net change in chemotherapy recommendations or decisions pre-/post-test ranged from an increase of one percent to a decrease of 23 percent among UK studies, and a decrease of zero percent to 64 percent across European studies.
The studies included in the review suggest that all of the tests can provide prognostic information on the risk of relapse; however results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence for prediction of chemotherapy benefit.
The rise of China and other great powers raises important questions about the persistence and stability of the 'liberal international order'. This book provides a new perspective on these questions by offering a novel theory of revisionist challenges to international order. It argues that rising powers sometimes seem to face the condition of 'status immobility', which activates social psychological and domestic political forces that push them toward lashing out in protest against status quo rules, norms, and institutions. Ward shows that status immobility theory illuminates important but often-overlooked dynamics that contributed to the most significant revisionist challenges in modern history. The book highlights the importance of status in world politics, and further advances a new understanding of this important concept's role in foreign policy. This book will be of interest to researchers in international politics and security, especially those interested in great power politics, status, power transitions, revisionism, and order.