Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5–15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL. Patients with IGH-CRLF2 were older (14 y vs. 4 y, P < .001), while the incidence of CRLF2-r among Down syndrome patients was high (50/161, 31%). CRLF2-r co-occurred with primary chromosomal rearrangements but the majority (111/161, 69%) had B-other ALL. Copy number alteration (CNA) profiles were similar to B-other ALL, although CRLF2-r patients harbored higher frequencies of IKZF1 (60/138, 43% vs. 77/1351, 24%) and BTG1 deletions (20/138, 15% vs. 3/1351, 1%). There were significant differences in CNA profiles between IGH-CRLF2 and P2RY8-CRLF2 patients: IKZF1 (25/35, 71% vs. 36/108, 33%, P < .001), BTG1 (11/35, 31% vs. 10/108, 9%, P =.004), and ADD3 deletions (9/19, 47% vs. 5/38, 13%, P =.008). A novel gene fusion, USP9X-DDX3X, was discovered in 10/54 (19%) of patients. Pathway analysis of the mutational profile revealed novel involvement for focal adhesion. Although the functional relevance of many of these abnormalities are unknown, they likely activate additional pathways, which may represent novel therapeutic targets

Beauty surveillance: the digital self-monitoring cultures of neoliberalism

This paper argues that ‘beauty apps’ are transforming the arena of appearance politics and foregrounds a theoretical architecture for critically understanding them. Informed by a feminist-Foucaultian framework, it argues that beauty apps offer a technology of gender which brings together digital self-monitoring and postfeminist modalities of subjecthood to produce an hitherto unprecedented regulatory gaze upon women that is marked by the intensification, extensification and psychologization of surveillance. The paper is divided into four sections. First it introduces the literature on digital self-tracking. Secondly it sets out our understanding of neoliberalism and postfeminism. Thirdly it looks at beauty and surveillance, before offering, in the final section, a typology of appearance apps. This is followed by a discussion of the modes of address/authority deployed in these apps – especially what we call ‘surveillant sisterhood’ - and the kinds of entrepreneurial subjectivity they constitute. The paper seeks to make a contribution to feminist surveillance studies and argues that much more detailed research is needed to critically examine beauty apps

Seeking legitimacy through CSR: Institutional Pressures and Corporate Responses of Multinationals in Sri Lanka

Arguably, the corporate social responsibility (CSR) practices of multinational enterprises (MNEs) are influenced by a wide range of both internal and external factors. Perhaps most critical among the exogenous forces operating on MNEs are those exerted by state and other key institutional actors in host countries. Crucially, academic research conducted to date offers little data about how MNEs use their CSR activities to strategically manage their relationship with those actors in order to gain legitimisation advantages in host countries. This paper addresses that gap by exploring interactions between external institutional pressures and firm-level CSR activities, which take the form of community initiatives, to examine how MNEs develop their legitimacy-seeking policies and practices. In focusing on a developing country, Sri Lanka, this paper provides valuable insights into how MNEs instrumentally utilise community initiatives in a country where relationship-building with governmental and other powerful non-governmental actors can be vitally important for the long-term viability of the business. Drawing on neo-institutional theory and CSR literature, this paper examines and contributes to the embryonic but emerging debate about the instrumental and political implications of CSR. The evidence presented and discussed here reveals the extent to which, and the reasons why, MNEs engage in complex legitimacy-seeking relationships with Sri Lankan institutions

KRILLBASE: a circumpolar database of Antarctic krill and salp numerical densities, 1926–2016

Antarctic krill (Euphausia superba) and salps are major macroplankton contributors to Southern Ocean food webs and krill are also fished commercially. Managing this fishery sustainably, against a backdrop of rapid regional climate change, requires information on distribution and time trends. Many data on the abundance of both taxa have been obtained from net sampling surveys since 1926, but much of this is stored in national archives, sometimes only in notebooks. In order to make these important data accessible we have collated available abundance data (numerical density, no.

Exploring potential mechanisms involved in the relationship between eudaimonic wellbeing and nature connection

ArticleThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.A growing body of research demonstrates associations between nature connection and a wide variety of positive health and wellbeing outcomes. Yet, the interpretation of this research is restricted because underpinning mechanisms − particularly the psychological mechanisms of wellbeing enhancement as opposed to wellbeing restoration − remain largely unexplored. Understanding such mechanisms is important for theory development and for assisting policy-makers and urban planners to translate this theory into practice effectively. This essay examines the limitations in our current understanding of the psychological mechanisms involved in the relationship between nature connection and eudaimonic wellbeing. It also advances opportunities to move the field forward through exploring two potential mechanisms, namely satisfying the psychological need of relatedness and fostering intrinsic value orientation. These mechanisms may explain how an individual’s level of nature connection enhances their psychological wellbeing. Understanding such mechanisms could improve the implementation of targeted nature connection policies and interventions designed to enhance psychological wellbeing among complex urban populations with diverse needs

Molecular motors robustly drive active gels to a critically connected state

Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

A new approach to assessing the health benefit from obesity interventions in children and adolescents: the assessing cost-effectiveness in obesity project

OBJECTIVE: To report on a new modelling approach developed for the assessing cost-effectiveness in obesity (ACE-Obesity) project and the likely population health benefit and strength of evidence for 13 potential obesity prevention interventions in children and adolescents in Australia. METHODS: We used the best available evidence, including evidence from non-traditional epidemiological study designs, to determine the health benefits as body mass index (BMI) units saved and disability-adjusted life years (DALYs) saved. We developed new methods to model the impact of behaviours on BMI post-intervention where this was not measured and the impacts on DALYs over the child\u27s lifetime (on the assumption that changes in BMI were maintained into adulthood). A working group of stakeholders provided input into decisions on the selection of interventions, the assumptions for modelling and the strength of the evidence. RESULTS: The likely health benefit varied considerably, as did the strength of the evidence from which that health benefit was calculated. The greatest health benefit is likely to be achieved by the \u27Reduction of TV advertising of high fat and/or high sugar foods and drinks to children\u27, \u27Laparoscopic adjustable gastric banding\u27 and the \u27multi-faceted school-based programme with an active physical education component\u27 interventions. CONCLUSIONS: The use of consistent methods and common health outcome measures enables valid comparison of the potential impact of interventions, but comparisons must take into account the strength of the evidence used. Other considerations, including cost-effectiveness and acceptability to stakeholders, will be presented in future ACE-Obesity papers. Information gaps identified include the need for new and more effective initiatives for the prevention of overweight and obesity and for better evaluations of public health interventions

Growth and shrinkage in Antarctic krill Euphausia superba is sex-dependent

ABSTRACT: The ability of Antarctic krill Euphausia superba Dana to withstand the overwintering period is critical to their success. Laboratory evidence suggests that krill may shrink in body length during this time in response to the low availability of food. Nevertheless, verification that krill can shrink in the natural environment is lacking because winter data are difficult to obtain. One of the few sources of winter krill population data is from commercial vessels. We examined length-frequency data of adult krill (>35 mm total body length) obtained from commercial vessels in the Scotia-Weddell region and compared our results with those obtained from a combination of science and commercial sampling operations carried out in this region at other times of the year. Our analyses revealed body-length shrinkage in adult females but not males during overwinter, based on both the tracking of modal size classes over seasons and sex-ratio patterns. Other explanatory factors, such as differential mortality, immigration and emigration, could not explain the observed differences. The same pattern was also observed at South Georgia and in the Western Antarctic Peninsula. Fitted seasonally modulated von Bertalanffy growth functions predicted a pattern of overwintering shrinkage in all body-length classes of females, but only stagnation in growth in males. This shrinkage most likely reflects morphometric changes resulting from the contraction of the ovaries and is not necessarily an outcome of winter hardship. The sex-dependent changes that we observed need to be incorporated into life cycle and population dynamic models of this species, particularly those used in managing the fishery. KEY WORDS: Southern Ocean · Population dynamics · Production · Life cycle · Fisher

Sports Nutrition: What the Future may Bring

The field of sports nutrition is a dynamic one. Core competencies in exercise physiology, psychology, integrated metabolism and biochemistry are the initial parameters for a successful career in sports nutrition. In addition to the academic fundamentals, it is imperative that the sports nutritionist understand the sport in which our client participates. This sport specific understanding should manifest itself in fuel utilization, mechanics of movement, as well as psychological processes that motivate the participant to perform optimally. Sports nutrition as a field has grown substantially over the past 50 years, from glycogen loading to today's scientifically validated ergogenic aids. The last ten years has seen the largest advancement of sports nutrition, with the following areas driving much of the research: the effects of exercise on protein utilization, meal timing to maximize the anabolic response, the potential for ribose to benefit those engaged in high-energy repetitive sports, and creatine and its uses within athletics and medicine. The future of sports nutrition will dictate that we 1) collectively strive for a higher standard of care and education for counseling athletes and 2) integrate different disciplines. We are in an era of unprecedented growth and the new knowledge is constantly evolving. The International Society of Sports Nutrition (ISSN) will contribute to this exciting field in many ways, and we ask for your contribution by sharing your passion, stories, research, and life experiences with us

A dedicated caller for DUX4 rearrangements from whole-genome sequencing data

\ua9 The Author(s) 2024.Rearrangements involving the DUX4 gene (DUX4-r) define a subtype of paediatric and adult acute lymphoblastic leukaemia (ALL) with a favourable outcome. Currently, there is no ‘standard of care’ diagnostic method for their confident identification. Here, we present an open-source software tool designed to detect DUX4-r from short-read, whole-genome sequencing (WGS) data. Evaluation on a cohort of 210 paediatric ALL cases showed that our method detects all known, as well as previously unidentified, cases of IGH::DUX4 and rearrangements with other partner genes. These findings demonstrate the possibility of robustly detecting DUX4-r using WGS in the routine clinical setting