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The paper considers the emergence of Alternative Comedy in the 1980s, placing this development in the context of Marx's understanding of capitalist society and a critique of Adorno's notion of the ...

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in many biological processes, including the immune pathways that control bacterial, parasitic, and viral infections. Pathogens probably modify host miRNAs to facilitate successful infection, so they might be useful targets for vaccination strategies. There are few data on differentially expressed miRNAs in the black-legged tick

RNAi is an evolutionarily fluid mechanism with dramatically different activities across animal phyla. One major group where there has been little investigation is annelid worms. Here, the small RNAs of the polychaete developmental model

This paper seeks to problematise the historical significance of the EU for British governing strategy with reference to immigration policy and the concept of depoliticisation. Situating British governing strategy in terms of the crisis-prone nature of capitalist society, this paper argues that British immigration policy has been depoliticised through, initially, the invocation of globalisation and, more recently, the EU. Through this strategy, the British state has been able to repeatedly claim that immigration policy is largely out of its hands, as they have no control over workers wishing to enter Britain looking for work. This paper makes three claims: firstly, immigration policy has been used as a means by both Conservative and Labour governments to manage inflation and labour; secondly, successive governments have sought to depoliticise immigration policy through reference to external forces; thirdly, this strategy of depoliticisation ultimately failed, politicising Britain’s relationship with the EU and creating conditions for Britain’s exit from the EU.

Background Following the initial identification of the 2019 coronavirus disease (covid-19), the subsequent months saw substantial increases in published biomedical research. Concerns have been raised in both scientific and lay press around the quality of some of this research. We assessed clinical research from major clinical journals, comparing methodological and reporting quality of covid-19 papers published in the first wave (here defined as December 2019 to May 2020 inclusive) of the viral pandemic with non-covid papers published at the same time. Methods We reviewed research publications (print and online) from The BMJ, Journal of the American Medical Association (JAMA), The Lancet, and New England Journal of Medicine, from first publication of a covid-19 research paper (February 2020) to May 2020 inclusive. Paired reviewers were randomly allocated to extract data on methodological quality (risk of bias) and reporting quality (adherence to reporting guidance) from each paper using validated assessment tools. A random 10% of papers were assessed by a third, independent rater. Overall methodological quality for each paper was rated high, low or unclear. Reporting quality was described as percentage of total items reported. Results From 168 research papers, 165 were eligible, including 54 (33%) papers with a covid-19 focus. For methodological quality, 18 (33%) covid-19 papers and 83 (73%) non-covid papers were rated as low risk of bias, OR 6.32 (95%CI 2.85 to 14.00). The difference in quality was maintained after adjusting for publication date, results, funding, study design, journal and raters (OR 6.09 (95%CI 2.09 to 17.72)). For reporting quality, adherence to reporting guidelines was poorer for covid-19 papers, mean percentage of total items reported 72% (95%CI:66 to 77) for covid-19 papers and 84% (95%CI:81 to 87) for non-covid. Conclusions Across various measures, we have demonstrated that covid-19 research from the first wave of the pandemic was potentially of lower quality than contemporaneous non-covid research. While some differences may be an inevitable consequence of conducting research during a viral pandemic, poor reporting should not be accepted.

The relationship between Marxism and imperialism has been established since the writings of Marx himself. Particularly in Capital, Volume I, Marx discusses the international division of labour caused by the expansion of capital in Ch.15, English capital in Ireland in Ch.25, as well as engaging with a theory of colonialism in Ch.33 ([1867] 1992a). Marx’s own views on both colonialism and imperialism have been well discussed in critical analysis of both his well- and lesser-known texts, many of which are presented in the compendium text ‘On Colonialism’ (Marx & Engels 2001; see, also, Pradella 2013; Nimtz 2002). However, the study of imperialism post-Marx grew from a belief that, while some analysis of imperialism was present in the works of Marx, a dedicated analysis of the state and the international sphere had been left at an embryonic stage. This is broadly true but this view has received criticism based on historiographical analysis of both Marx and the earliest authors on imperialism (Pradella 2013). The phenomenon of imperialism, while still discussed by Marx in a number of instances, was not given the same sustained critical attention as other issues in Marx’s work. This is the point at which Marxism’s engagement with imperialism becomes more profound and substantial. Imperialism, therefore, to Marxism has always been a ‘problem’ of some form. Indeed, the ‘problem’ of imperialism derives from a number of perceived sources: gaps in Marx’s own writing; an explanation for why capitalism endures; an account of the phenomenon of globalisation. It is the contention of this chapter, then, that the on-going relationship between Marxism and imperialism reveals one of Marxism’s main strengths, and its clear weaknesses. It reveals Marxism’s capacity to explain new phenomena coupled with a rigorous and critical method; however, it also reveals a reliance on systemic explanations for contingent developments, and a considerable partisanship between radical thinkers. This relationship between Marxism and imperialism therefore begins early in the 20th Century with the work of the ‘classical’ authors of imperialism, building on the work of Marx and critiquing extant understandings of imperialism, particularly John Hobson’s. This chapter charts the origins of this relationship and its various iterations throughout the 20th century until the present. This relationship has, fundamentally, changed very little, deriving largely from Marx’s own work, and the work of the first Marxist theorists of imperialism. Indeed, the relationship is iterative rather than developmental, with particular ideas within Marxist theories of imperialism recurring perpetually. Most notably, the overarching power of Finance, or monopoly capital, within capitalism, and the idea of imperialism as a qualitatively distinct ‘stage’ of capitalist development are extremely powerful ideas within the tradition of Marxist theories of imperialism. The paper will be split into three sections according to various ‘phases’ of Marxist thought on imperialism: firstly, the ‘classical’ Marxists, from Hilferding to Lenin; secondly, the ‘neo- Colonialist’ thinkers; and finally, the ‘New’ imperialists.

Micronuclei (MN) originate from whole chromosomes or chromosome fragments that lag behind during cell division and fail to be incorporated into one of the two main nuclei. As a result, scoring MN using the well-established in vitro micronucleus assay evaluates the ability of chemicals or other agents to induce DNA damage. This technique is typically performed by manual microscopy, which can be time-consuming and prone to variability. Additionally, automated methods lack cytoplasmic visualization when using slide-scanning microscopy, and conventional flow cytometry doesn’t provide visual confirmation of MN. The ImageStream®X Mk II (ISX) imaging flow cytometer combines the high-resolution imagery of microscopy with conventional flow cytometry’s speed and statistical robustness in a single system. Previously, we developed a rapid and automated MN assay based on high-throughput image capture and feature-based image analysis using IDEAS® Software. However, the feature-based analysis was not readily applicable to multiple cell lines and chemicals, so we developed a deep learning method based on convolutional neural networks to score imaging flow cytometry data in both the cytokinesis-blocked and unblocked versions of the MN assay using Amnis® AI Software. Our current study validates our previously established assay and analyses using three different chemicals (Mitomycin C, Cyclophosphamide, and Eugenol) and three different cell lines (TK6, L5178Y, CHO-K1). Here, we demonstrate how using Amnis AI to score imagery acquired on the ISX provides a rapid and fully automated in vitro MN assay with improved accuracy, reproducibility, and time-to-results in toxicity and biodosimetry applications across multiple cell lines.

IntroductionSynthesis of clinical effectiveness is a well-established component of health technology assessment (HTA) combining data from multiple trials to obtain an overall pooled estimate of clinical effectiveness, which may inform an associated economic evaluation. Time-to-event outcomes are often synthesized using effect measures from Cox proportional hazards models assuming a constant hazard ratio over time. However, where treatment effects vary over time an assumption of proportional hazards is not always valid. Several methods have been proposed for synthesizing time-to-event outcomes in the presence of non-proportional hazards. However, guidance on choosing between these methods and the implications for HTA is lacking.MethodsWe applied five methods for estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption to a network of melanoma trials, reporting overall survival: restricted mean survival time, an accelerated failure time generalized gamma model, piecewise exponential, fractional polynomial and Royston-Parmar models. We conducted a simulation study to compare these five methods. Simulated individual patient data was generated from a mixture Weibull distribution assuming a treatment-time interaction. Each simulated meta-analysis consisted of five trials with varying numbers of patients and length of follow-up across trials. For each model fitted to each dataset, we calculated the restricted mean survival time at the end of observed follow-up and following extrapolation to a 20-year time horizon.ResultsAll models fitted the melanoma data reasonably well with some variation in the treatment rankings and differences in the survival curves. The simulation study demonstrated the potential for different conclusions from different modelling approaches.ConclusionsThe restricted mean survival time, generalized gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can all accommodate non-proportional hazards and differing lengths of trial follow-up within an evidence synthesis of time-to-event outcomes. Further work is needed in this area to extend the simulation study to the network meta-analysis setting and provide guidance on the key considerations for informing model choice for the purposes of HTA.

IntroductionThe sequential use of alternative treatments for chronic conditions represents a complex, dynamic intervention pathway; previous treatment and patient characteristics affect both choice and effectiveness of subsequent treatments. Evidence synthesis methods that produce the least biased estimates of treatment-sequencing effects are required to inform reliable clinical and policy decision-making. A comprehensive review was conducted to establish what existing methods are available, outline the assumptions they make, and identify their shortcomings.MethodsThe review encompassed both meta-analytic techniques and decision-analytic modelling, any disease condition, and any type of treatment sequence, but not diagnostic tests, screening, or treatment monitoring. It focused on the estimation of clinical effectiveness and did not consider the impact of treatment sequencing on the estimation of costs or utility values.ResultsThe review included ninety-one studies. Treatment-sequencing is usually dealt with at the decision-modelling stage and is rarely addressed using evidence synthesis methodology for clinical effectiveness. Most meta-analyses are of discrete treatments, sometimes stratified by line of therapy. Prospective sequencing trials are scarce. In their absence, there is no single best way to evaluate treatment sequences, rather there is a range of approaches, each of which has advantages and disadvantages and is influenced by the evidence available and the decision problem. Due to the scarcity of data on sequential treatments, modelling studies generally apply simplifying assumptions to data on discrete treatments. A taxonomy for all possible assumptions was developed, providing a unique resource to aid the critique of decision-analytic models.ConclusionsThe evolution of network meta-analysis in HTA demonstrates that clinical and policy decision-making should account for the multiple treatments available for many chronic conditions. However, treatment-sequencing has yet to be accounted for within clinical evaluations. Economic modelling is often based on the simplifying assumption of treatment independence. This can lead to misrepresentation of the true level of uncertainty, potential bias in estimating the effectiveness and cost effectiveness of treatments and, eventually, the wrong decision.

IntroductionNetwork meta-analysis (NMA) is a key methodology for comparing the effectiveness of multiple interventions or treatments simultaneously. This project aimed to ascertain current methods and visualizations for treatment ranking within an NMA framework and to subsequently develop a novel graphic within MetaInsight (an interactive NMA web application), to aid clinicians and stakeholders when making decisions regarding the “best” intervention(s) for their patient(s).MethodsCurrent literature on the methodology or visualization of treatment ranking published in the last 10 years was collated and studied. Based on the literature, a novel graphical visualization was developed using RShiny (RStudio, PBC) and integrated within MetaInsight, which is currently hosted on shinyapps.io.ResultsBayesian analyses produce rank probabilities from which mean or median rank and surface under the cumulative ranking curve can be calculated. For frequentist analyses the p-value is available. The simpler methods may be easier to interpret, but they are often more unstable and do not encompass the whole analysis (and vice versa). To aid interpretation and facilitate sensitivity analysis, an interactive graphic was developed that presents rankings alongside treatment effect and study quality results.ConclusionsTreatment ranking is useful, but the results should be interpreted cautiously, and the visualization should be transparent and all-encompassing. A ‘living’ version of MetaInsight, with treatment ranking, would allow interested parties to follow the evidence base as it grows.

IntroductionThe use of real-world data, as an alternative to randomized controlled trials, is becoming increasingly common in the evaluation of new health technologies. With this rise in real-world literature, such data will also enter evidence synthesis models. While it can be beneficial to utilize data from all available sources, this can introduce the problem of double-counting of participants.MethodsUsing a number of case-studies, we discuss and illustrate various issues around double-counting. These include synthesis of studies using the same database or the same subset of participants, overlapping use of intervention arms across studies and the use of registry data from the participants overlapping with those in randomized controlled trials. The implications in research are considered along with common methods used currently to overcome these issues.ResultsDouble-counting of participants in evidence synthesis can artificially inflate precision, potentially leading to inappropriate conclusions. Common methods currently used to help mitigate the impact of double-counting includes stratifying analysis to different timelines, using the most comprehensive study in the evidence synthesis model or using the study that has the largest sample size. However, in all of these cases, sensitivity analyses would need to be considered to ensure robust results.ConclusionsCurrently, there are no published guidelines on how to address the issue of double-counting. With the increased use of real-world data in evidence synthesis, double-counting has the potential to become a significant issue. Therefore, it is of significant importance that methodologies and guidelines are developed to address this.

This article seeks to review the recent incarnation of a long-standing engagement in international political economy (IPE) and critical theory between open Marxist perspectives (OMPs) and their critics. The article aims to identify the enduring relevance of this debate in order to think about the possibility and future of critical social inquiry in our time constructively. It criticises elements on both sides of the debate that no longer serve but rather hinder achieving this objective. We argue that the recent criticisms make a number of important constructive points that could help enhance the explanatory power of OMPs yet still portray the latter uncharitably. We propose to take the emphasis on openness in OMPs seriously as a scholarly and political orientation without immersing the debate with the charges of reductionism, instrumentalism, determinism and functionalism which are frequently raised by various versions of Marxism against one another—often to little avail.

The article focuses on Britain’s relationship with Malaya shortly before and after its independence from the British Empire. The article looks at the negotiations concerning the financial settlement prior to independence. Britain sought to keep Malaya within the sterling area at all costs, even after de jure convertibility had been achieved, due to its high dollar earning capacity, which remained important due to persistent trade deficits with the US from the end of the Second World War. The article argues that this settlement, while seemingly very generous for an independent Malaya, was still very much intended to maintain Britain’s role within the global economy, to ensure sterling’s status as an international currency and to support conditions for British economic growth.

This article develops a critical engagement with the politics of British satire. After first engaging the mainstream critique of satire—that it promotes cynicism and apathy by portraying politicians in stereotypically corrupt terms—we develop a performative approach to comedy as an everyday vernacular of political life. Beyond a focus on ‘impact’, we suggest that satire can be read as an everyday form of political reflection that performs within a social context. This argument yields an image of Morris, Iannucci and Brooker as important critics of contemporary British politics, a point which we explore through their interventions on media form, political tragedy and political agency.

Antisense morpholino oligonucleotides have been commonly used in zebrafish to inhibit mRNA function, either by inhibiting pre-mRNA splicing or by blocking translation initiation. Even with the advent of genome editing by CRISP/Cas9 technology, morpholinos provide a useful and rapid tool to knockdown gene expression. This is especially true when dealing with multiple alleles and large gene families where genetic redundancy can complicate knockout of all family members. miRNAs are small noncoding RNAs that are often encoded in gene families and can display extensive genetic redundancy. This redundancy, plus their small size which can limit targeting by CRISPR/Cas9, makes morpholino-based strategies particularly attractive for inhibition of miRNA function. We provide the rationale, background, and methods to inhibit miRNA function with antisense morpholinos during early development and in the adult retina in zebrafish.

The purpose of this paper is to provide the basis for a theory of imperialism that is consonant with open Marxism. The paper argues that accounts of imperialism heretofore have been contingent and focused on the appearance of imperialism, and spent little time considering its essence as a manifestation of the state’s power and desire to maintain the circuit of capital both nationally and internationally. The paper seeks to show that open Marxism is well placed to achieve this, and to move towards an idea of an open Marxist theory of imperialism.

A prominent theme in scholarly analyses of contemporary international affairs concerns the extent to which the unrivalled power and activities of the United States can be said to constitute a form of imperialism. Typically, the contours of this debate center on the ostensible differences between “old” and “new” varieties of imperialist practice. Yet the concept of “new imperialism” remains one on which little consensus exists. Wide differences of opinion on its origins, dynamics, and characteristics are evident, as is an analytical bifurcation between distinct “economic” and “geopolitical” explanations. This absence of conceptual unity leads to accounts of new imperialist strategy that are partial, limited, and incomplete. If the theoretical value of new imperialism is to be realized, a more holistic approach is needed. To this end, some of the key differences between the contexts of new and old imperialism are explored.

Approaches to depoliticisation have tended to focus on its use as a domestic strategy. The purpose of depoliticisation, whether discourse-, rule-, or institution-based, is to distance or limit the political character of a particular issue or policy. Where the literature on depoliticisation tends to be lacking is in its international role. This paper seeks to explore how imperialist policies, that is policies intended to dominate one state by another, have been depoliticized by being channeled through technically- managed or apparently economic institutions. The paper situates an account of depoliticisation in terms of the nature of global capitalist society, and seeks to explore how imperial strategy was depoliticized through the Sterling Area. The paper looks at an episode in British-Malayan relations in which the apolitical character of the Sterling Area is brought into question. The purpose of this strategy of depoliticisation, as with its domestic instances, is to remove accountability from state managers, provide them with greater governing autonomy and to limit social instability, while at the same time trying to remove barriers for capital accumulation on a global scale.

The chapter will provide an overview of the political economy of Britain during the first half of the 20th century, focusing on Britain’s position in the global capitalist economy and its continued relative economic decline. The chapter will also provide historical accounts of both the Sterling Area and Malaya. This chapter intends to provide a historical background to, and so contextualise, the thesis’ main narrative in the subsequent chapters. In so doing, it is the intention of this chapter to avoid the periodisation of history, as well as to illustrate that the nature of the post-war relationship between Britain and Malaya finds its origins in Britain’s relative economic decline.

This chapter establishes the theoretical framework for the analysis of Britain’s relationship with Malaya. It accomplishes this by first providing an assessment of the current scholarship on British imperial economic relations. These accounts are argued to be problematic and an alternative, open Marxist approach is developed. This approach argues that imperialism is a relationship between two states, undertaken as part of a strategy designed by state managers of the dominant state with a view to achieving adequate conditions for the reproduction of capitalist social relations.

This chapter will examine British responses to the Dollar Drain and the Convertibility Crisis with respect to the Sterling Area and, and most particularly, the British relationship with Malaya. One aspect of this chapter, as with the other two empirical chapters, is to emphasise the reliance of the British state on the Sterling Area, which was the sole means of multilateral trade outside of the dollar area1 and, as such, vital to the reconstruction of global trade after the Second World War, and to the reconstruction of the British economy.

This chapter covers the period from 1950 to 1955 in Britain’s relationship with Malaya. This chapter, as with the preceding chapter, charts continuity in this relationship both within this period, and from the last.

This chapter charts Britain’s negotiations with Malaya concerning its eventual independence, including Malaya’s relationship with the Sterling Area, its exchange controls, membership of the International Monetary Fund (IMF) and plans for the future development of Malaya.