Capitals and commitment. The case of a local learning and employment network.

This article draws on research undertaken with a Local Learning and Employment Network (LLEN) in the state of Victoria, Australia. LLEN are networks that were implemented by the state government in 2001 to undertake community capacity building through which the outcomes of young people aged 15-19 in education, training and employment would be enhanced. In 2008, in the context of an enhanced federal commitment to social inclusion through ‘joining-up’, the Victorian experience provides insights on the implications of such policy initiatives. Drawing on Bourdieu’s discussion of the forms of capital and Granovetter’s notion of the strength of weak ties, I argue that stores of economic, cultural and social capital as outlined by Bourdieu were necessary, but insufficient, for LLEN to achieve the objectives with which they were charged given the failure of government to follow through on the implications of its policies. I argue for a commitment on the part of all stakeholders to realise the potential of ‘joining-up’

The prevalence of axial spondyloarthritis in the UK: a cross-sectional cohort study

Background: Accurate prevalence data are important when interpreting diagnostic tests and planning for the health needs of a population, yet no such data exist for axial spondyloarthritis (axSpA) in the UK. In this cross-sectional cohort study we aimed to estimate the prevalence of axSpA in a UK primary care population. Methods: A validated self-completed questionnaire was used to screen primary care patients with low back pain for inflammatory back pain (IBP). Patients with a verifiable pre-existing diagnosis of axSpA were included as positive cases. All other patients meeting the Assessment of SpondyloArthritis international Society (ASAS) IBP criteria were invited to undergo further assessment including MRI scanning, allowing classification according to the European Spondyloarthropathy Study Group (ESSG) and ASAS axSpA criteria, and the modified New York (mNY) criteria for ankylosing spondylitis (AS). Results: Of 978 questionnaires sent to potential participants 505 were returned (response rate 51.6 %). Six subjects had a prior diagnosis of axSpA, 4 of whom met mNY criteria. Thirty eight of 75 subjects meeting ASAS IBP criteria attended review (mean age 53.5 years, 37 % male). The number of subjects satisfying classification criteria was 23 for ESSG, 3 for ASAS (2 clinical, 1 radiological) and 1 for mNY criteria. This equates to a prevalence of 5.3 % (95 % CI 4.0, 6.8) using ESSG, 1.3 % (95 % CI 0.8, 2.3) using ASAS, 0.66 % (95 % CI 0.28, 1.3) using mNY criteria in chronic back pain patients, and 1.2 % (95 % CI 0.9, 1.4) using ESSG, 0.3 % (95 % CI 0.13, 0.48) using ASAS, 0.15 % (95 % CI 0.02, 0.27) using mNY criteria in the general adult primary care population. Conclusions: These are the first prevalence estimates for axSpA in the UK, and will be of importance in planning for the future healthcare needs of this population. Trial registration: Current Controlled Trials ISRCTN7687321

A prospective study to assess the value of MMP-9 in improving the appropriateness of urgent referrals for colorectal cancer

Background Bowel cancer is common and is a major cause of death. Most people with bowel symptoms who meet the criteria for urgent referral to secondary care will not be found to have bowel cancer, and some people who are found to have cancer will have been referred routinely rather than urgently. If general practitioners could better identify people who were likely to have bowel cancer or conditions that may lead to bowel cancer, the pressure on hospital clinics may be reduced, enabling these patients to be seen more quickly. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with such conditions, and this can be measured from a blood sample. This study aims to find out whether measuring MMP-9 levels could improve the appropriateness of urgent referrals for patients with bowel symptoms. Methods People aged 18 years or older referred to a colorectal clinic will be asked to complete a questionnaire about symptoms, recent injuries or chronic illnesses (these can increase the level of matrix metalloproteinases) and family history of bowel cancer. A blood sample will be taken from people who consent to take part to assess MMP-9 levels, and the results of examination at the clinic and/or investigations arising from the clinic visit will be collected from hospital records. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the resulting diagnosis. The combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined. Discussion Although guidelines are in place to facilitate referrals to colorectal clinics, symptoms alone do not adequately distinguish people with malignancy from people with benign conditions. This study will establish whether MMP-9 could assist this process. If this were the case, measurement of MMP-9 levels could be used by general practitioners to assist in the identification of people who were most likely to have bowel cancer or conditions that may lead to bowel cancer, and who should, therefore, be referred most urgently to secondary car

PLK1 inhibitors as a new targeted treatment for adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited treatment options. Polo-like kinase 1 (PLK1) is a promising drug target; PLK1 inhibitors (PLK1i) have been investigated in solid cancers and are more effective in TP53-mutated cases. We evaluated PLK1 expression in ACC samples and the efficacy of two PLK1i in ACC cell lines with different genetic backgrounds. PLK1 protein expression was investigated by immunohistochemistry in tissue samples and correlated with clinical data. The efficacy of rigosertib (RGS), targeting RAS/PI3K, CDKs and PLKs, and poloxin (Pol), specifically targeting the PLK1 polo-box domain, was tested in TP53-mutated NCI-H295R, MUC-1, and CU-ACC2 cells and in TP53 wild-type CU-ACC1. Effects on proliferation, apoptosis, and viability were determined. PLK1 immunostaining was stronger in TP53-mutated ACC samples vs wild-type (P = 0.0017). High PLK1 expression together with TP53 mutations correlated with shorter progression-free survival (P= 0.041). NCI-H295R showed a time- and dose-dependent reduction in proliferation with both PLK1i (P< 0.05at 100 nM RGS and 30 µM Pol). In MUC-1, a less pronounced decrease was observed (P< 0.05at 1000 nM RGS and 100 µM Pol). 100 nM RGS increased apoptosis in NCI-H295R (P< 0.001), with no effect on MUC-1. CU-ACC2 apoptosis was induced only at high concentrations (P < 0.05 at 3000 nM RGS and 100 µM Pol), while proliferation decreased at 1000 nM RGS and 30 µM Pol. CU-ACC1 proliferation reduced, and apoptosis increased, only at 100 µM Pol. TP53-mutated ACC cell lines demonstrated better response to PLK1i than wild-type CU-ACC1. These data suggest PLK1i may be a promising targeted treatment of a subset of ACC patients, pre-selected according to tumour genetic signature

Differential roles of CCL2 and CCR2 in host defense to coronavirus infection.

The CC chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1) is important in coordinating the immune response following microbial infection by regulating T cell polarization as well as leukocyte migration and accumulation within infected tissues. The present study examines the consequences of mouse hepatitis virus (MHV) infection in mice lacking CCL2 (CCL2(-/-)) in order to determine if signaling by this chemokine is relevant in host defense. Intracerebral infection of CCL2(-/-) mice with MHV did not result in increased morbidity or mortality as compared to either wild type or CCR2(-/-) mice and CCL2(-/-) mice cleared replicating virus from the brain. In contrast, CCR2(-/-) mice displayed an impaired ability to clear virus from the brain that was accompanied by a reduction in the numbers of antigen-specific T cells as compared to both CCL2(-/-) and wild-type mice. The paucity in T cell accumulation within the central nervous system (CNS) of MHV-infected CCR2(-/-) mice was not the result of either a deficiency in antigen-presenting cell (APC) accumulation within draining cervical lymph nodes (CLN) or the generation of virus-specific T cells within this compartment. A similar reduction in macrophage infiltration into the CNS was observed in both CCL2(-/-) and CCR2(-/-) mice when compared to wild-type mice, indicating that both CCL2 and CC chemokine receptor 2 (CCR2) contribute to macrophage migration and accumulation within the CNS following MHV infection. Together, these data demonstrate that CCR2, but not CCL2, is important in host defense following viral infection of the CNS, and CCR2 ligand(s), other than CCL2, participates in generating a protective response

Evidence for the commission on race and ethnic disparities

This report summarizes the best-available evidence concerning race inequities in the English education system. We outline the scale of race inequity (especially in terms of achievement and exclusions from school) and explore the powerful, and often hidden, operation of institutional racism. Among the key issues we address are: • the complex and extensive role of racism as a factor operating across the system; • the dangers of ‘garbage can’ statistical modelling where statisticians mistakenly imagine that they can identify the separate operation of racism outside the intertwined effects of multiple other factors which are, themselves, shaped by patterns of race inequity. • the myth of the ‘worst’ performing White working class: we show how the misuse of limited data has perpetuated a view of White children as race victims and ignored stark race inequities that impact several minoritized groups, including students of Gypsy/Roma, Black Caribbean, Mixed Race (Black Caribbean/White) and Pakistani heritage. • the operation of racism in schools and classrooms, affecting minoritized children and limiting the chances of minoritized teachers and school leaders. • the need for positive antiracist action across the system, including the role of OFSTED (the schools inspectorate), initial teacher education, and the role of policymakers to finally take seriously the endemic nature of race inequity. The document was submitted to the Commission on Race and Ethnic Disparities in 2020. We were not contacted by the Commission to discuss our analysis or the evidence that we summarize. Their report, published in March 2021, signals the gulf between the reality of racism in education and official fantasies of White victimhood and a world where Britain is imagined to be a ‘beacon’ of multi-ethnic harmony

The use of herbal medicines by people with cancer: a cross-sectional survey

BACKGROUND: A large proportion of cancer patients are estimated to use herbal medicines, but data to substantiate this are lacking. This study aimed to investigate the prevalence of herbal medicine use among cancer patients in the West Midlands, and determine the characteristics predicting herbal medicine use. METHODS: A cross-sectional survey of oncology patients (n=1498) being followed up at a hospital in Coventry was undertaken. Recipients were asked about herbal medicine use since their cancer diagnosis, and the association between sociodemographic and cancer-related characteristics and herbal medicine use was evaluated. RESULTS: A total of 1134 responses were received (75.7%). The prevalence of herbal medicine use was 19.7% (95% CI: 17.4-22.1; n=223). Users were more likely to be affluent, female, and aged under 50 years. Usage increased with time since cancer diagnosis (X(2) for trend=4.63; P=0.031). A validation data set, derived from a survey of oncology patients in Birmingham (n=541) with differing socioeconomic characteristics showed no significant difference in estimated prevalence (16.6%; 95% CI: 11.9-22.2). CONCLUSION: A substantial number of people with cancer are likely to be taking herbal medicines. Understanding the self-medication behaviours of these individuals is essential if health-care professionals are to support treatment adherence and avoid unwanted pharmacological interactions