Making a difference in education: What the evidence says

Robert Cassen, Sandra McNally and Anna Vignoles write that, as regards reducing the social gap, there is evidence that points to good potential in redirecting educational spending. They also argue for introducing fewer policy initiatives into the education system without proper evaluation

Do management practices matter in further education?

Further education and sixth form colleges are key institutions for facilitating skill acquisition among 16–19 year olds in the UK. They enrol half a school cohort after completion of their lower secondary education, and this includes a disproportionate number from low-income backgrounds. Yet little is known about what could improve performance in these institutions. We conduct the world's first management practices survey in such institutions, and match this to administrative longitudinal data on over 40,000 students. Value-added regressions with rich controls suggest that structured management matters for educational outcomes, especially for students from low-income backgrounds. For this group, in a hypothetical scenario where an individual is moved from a college at the 10th percentile of management practices to the 90th, this would be associated with 8% higher probability of achieving a good high school qualification, nearly half of the educational gap between those from poor and non-poor backgrounds. Hence improving management practices may be an important channel for reducing inequalities

Discovering Knitting at the Regent Street Polytechnic, 1898‐1948

The archive concerning the development and activities of the Regent Street Polytechnic held at the University of Westminster, London is an especially rich source of information concerning knitting, its changing status as craft, leisure activity, charitable work, and morale booster. Charting knitting's role in both world wars, the Boer War, and as a vital mainstay of the Royal National Mission to Deep Sea Fishermen, the text provides a unique insight into the spaces occupied by knitting within an educational institution and how it provided a voice and increased instrumentality for women within that establishment at the end of the nineteenth and beginning of the twentieth centuries

Decitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer

Aberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation. Importantly, DAC treatment increases ICN1 expression (the active intracellular domain of NOTCH1) significantly inhibiting cell proliferation and causing changes in cell size inducing morphological alterations reminiscent of senescence. These changes were not associated with β-galactosidase activity or increased p16 levels, but instead were associated with substantial IL-6 release. Increased IL-6 release was observed in both DAC-treated and ICN1 overexpressing cells as compared to control cells. Exogenous IL-6 expression was associated with a similar enlarged cell morphology that was rescued by the addition of a monoclonal antibody against IL-6. Treatment with DAC, overexpression with ICN1 or addition of exogenous IL-6 showed CK5 reduction, a surrogate marker of differentiation. Overall this study suggests that in MIBC cells, DNA hypomethylation increases NOTCH1 expression and IL-6 release to induce CK5-related differentiation.Fil: Ramakrishnan, Swathi. Roswell Park Cancer Institute; Estados UnidosFil: Hu, Qiang. Roswell Park Cancer Institute; Estados UnidosFil: Krishnan, Nithya. Roswell Park Cancer Institute; Estados UnidosFil: Wang, Dan. Roswell Park Cancer Institute; Estados UnidosFil: Smit, Evelyn. Roswell Park Cancer Institute; Estados UnidosFil: Granger, Victoria. Roswell Park Cancer Institute; Estados UnidosFil: Rak, Monika. Jagiellonian University; PoloniaFil: Attwood, Kristopher. Roswell Park Cancer Institute; Estados UnidosFil: Johnson, Candace. Roswell Park Cancer Institute; Estados UnidosFil: Morrison, Carl. Roswell Park Cancer Institute; Estados UnidosFil: Pili, Roberto. Indiana University; Estados UnidosFil: Chatta, Gurkamal. Roswell Park Cancer Institute; Estados UnidosFil: Guru, Khurshid. Roswell Park Cancer Institute; Estados UnidosFil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: McNally, Lacey. University of Louisville; Estados UnidosFil: Wang, Jianmin. Roswell Park Cancer Institute; Estados UnidosFil: Woloszynska-Read, Anna. Roswell Park Cancer Institute; Estados Unido

Strong pathogen competition in neonatal gut colonisation

Opportunistic bacterial pathogen species and their strains that colonise the human gut are generally understood to compete against both each other and the commensal species colonising this ecosystem. Currently we are lacking a population-wide quantification of strain-level colonisation dynamics and the relationship of colonisation potential to prevalence in disease, and how ecological factors might be modulating these. Here, using a combination of latest high-resolution metagenomics and strain-level genomic epidemiology methods we performed a characterisation of the competition and colonisation dynamics for a longitudinal cohort of neonatal gut microbiomes. We found strong inter- and intra-species competition dynamics in the gut colonisation process, but also a number of synergistic relationships among several species belonging to genus Klebsiella, which includes the prominent human pathogen Klebsiella pneumoniae. No evidence of preferential colonisation by hospital-adapted pathogen lineages in either vaginal or caesarean section birth groups was detected. Our analysis further enabled unbiased assessment of strain-level colonisation potential of extra-intestinal pathogenic Escherichia coli (ExPEC) in comparison with their propensity to cause bloodstream infections. Our study highlights the importance of systematic surveillance of bacterial gut pathogens, not only from disease but also from carriage state, to better inform therapies and preventive medicine in the future.Peer reviewe

Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer

Lysine-specific demethylase 6A (KDM6A) and members of the Switch/Sucrose Non-Fermentable (SWI/SNF) family are known to counteract the activity of Enhancer of Zeste Homolog 2 (EZH2), which is often overexpressed and is associated with poor prognosis in muscle-invasive bladder cancer. Here we provide evidence that alterations in chromatin modifying enzymes, including KDM6A and members of the SWI/SNF complex, are frequent in muscle-invasive bladder cancer. We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. We reveal a novel mechanism of action of EZH2 inhibition, alone and in combination with cisplatin, which induces immune signaling with the largest changes observed in interferon gamma (IFN-γ). This upregulation is a result of activated natural killer (NK) signaling as demonstrated by the increase in NK cell-associated genes MIP-1α, ICAM1, ICAM2, and CD86 in xenografts treated with EZH2 inhibitors. Conversely, EZH2 inhibition results in decreased expression of pluripotency markers, ALDH2 and CK5, and increased cell death. Our results reveal a novel sensitivity of muscle-invasive bladder cancer cells with KMD6A and SWI/SNF mutations to EZH2 inhibition alone and in combination with cisplatin. This sensitivity is mediated through increased NK cell-related signaling resulting in tumor cell differentiation and cell death.Fil: Ramakrishnan, Swathi. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Granger, Victoria. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Rak, Monica. Jagiellonian University; PoloniaFil: Hu, Qiang. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Attwood, Kristopher. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Aquila, Lanni. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Krishnan, Nithya. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Osiecki, Rafal. Medical University Of Warsaw; PoloniaFil: Azabdaftari, Gissou. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Guru, Khurshid. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Chatta, Gurkamal. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: McNally, Lacey. Wake Forest Comprehensive Cancer Center; Estados UnidosFil: Ohm, Joyce. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Wang, Jianmin. Roswell Park Comprehensive Cancer Center; Estados UnidosFil: Woloszynska-Read, Anna. Roswell Park Comprehensive Cancer Center; Estados Unido

c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells

During thymopoiesis, a unique program of gene expression promotes the development of CD4 regulatory T (T reg) cells. Although Foxp3 maintains a pattern of gene expression necessary for T reg cell function, other transcription factors are emerging as important determinants of T reg cell development. We show that the NF-κB transcription factor c-Rel is highly expressed in thymic T reg cells and that in c-rel−/− mice, thymic T reg cell numbers are markedly reduced as a result of a T cell–intrinsic defect that is manifest during thymocyte development. Although c-Rel is not essential for TGF-β conversion of peripheral CD4+CD25− T cells into CD4+Foxp3+ cells, it is required for optimal homeostatic expansion of peripheral T reg cells. Despite a lower number of peripheral T reg cells in c-rel−/− mice, the residual peripheral c-rel−/− T reg cells express normal levels of Foxp3, display a pattern of cell surface markers and gene expression similar to those of wild-type T reg cells, and effectively suppress effector T cell function in culture and in vivo. Collectively, our results indicate that c-Rel is important for both the thymic development and peripheral homeostatic proliferation of T reg cells

Conventional inactivated bivalent H5/H7 vaccine prevents viral localization in muscles of turkeys infected experimentally with low pathogenic avian influenza and highly pathogenic avian influenza H7N1 isolates

Highly pathogenic avian influenza (HPAI) viruses cause viraemia and systemic infections with virus replication in internal organs and muscles; in contrast, low pathogenicity avian influenza (LPAI) viruses produce mild infections with low mortality rates and local virus replication. There is little available information on the ability of LPAI viruses to cause viraemia or on the presence of avian influenza viruses in general in the muscles of infected turkeys. The aim of the present study was to determine the ability of LPAI and HPAI H7N1 viruses to reach muscle tissues following experimental infection and to determine the efficacy of vaccination in preventing viraemia and meat localization. The potential of infective muscle tissue to act as a source of infection for susceptible turkeys by mimicking the practice of swill-feeding was also investigated. The HPAI virus was isolated from blood and muscle tissues of all unvaccinated turkeys; LPAI could be isolated only from blood of one bird and could be detected only by reverse transcriptasepolymerase chain reaction in muscles. In contrast, no viable virus or viral RNA could be detected in muscles of vaccinated/challenged turkeys, indicating that viral localization in muscle tissue is prevented in vaccinated birds

Modulation of multidrug-resistant clone success in <i>Escherichia coli</i> populations:a longitudinal, multi-country, genomic and antibiotic usage cohort study

BACKGROUND: The effect of antibiotic usage on the success of multidrug-resistant (MDR) clones in a population remains unclear. With this genomics-based molecular epidemiology study, we aimed to investigate the contribution of antibiotic use to Escherichia coli clone success, relative to intra-strain competition for colonisation and infection.METHODS: We sequenced all the available E coli bloodstream infection isolates provided by the British Society for Antimicrobial Chemotherapy (BSAC) from 2012 to 2017 (n=718) and combined these with published data from the UK (2001-11; n=1090) and Norway (2002-17; n=3254). Defined daily dose (DDD) data from the European Centre for Disease Prevention and Control (retrieved on Sept 21, 2021) for major antibiotic classes (β-lactam, tetracycline, macrolide, sulfonamide, quinolone, and non-penicillin β-lactam) were used together with sequence typing, resistance profiling, regression analysis, and non-neutral Wright-Fisher simulation-based modelling to enable systematic comparison of resistance levels, clone success, and antibiotic usage between the UK and Norway.FINDINGS: Sequence type (ST)73, ST131, ST95, and ST69 accounted for 892 (49·3%) of 1808 isolates in the BSAC collection. In the UK, the proportion of ST69 increased between 2001-10 and 2011-17 (p=0·0004), whereas the proportions of ST73 and ST95 did not vary between periods. ST131 expanded quickly after its emergence in 2003 and its prevalence remained consistent throughout the study period (apart from a brief decrease in 2009-10). The extended-spectrum β-lactamase (ESBL)-carrying, globally disseminated MDR clone ST131-C2 showed overall greater success in the UK (154 [56·8%] of 271 isolates in 2003-17) compared with Norway (51 [18·3%] of 278 isolates in 2002-17; p&lt;0·0001). DDD data indicated higher total use of antimicrobials in the UK, driven mainly by the class of non-penicillin β-lactams, which were used between 2·7-times and 5·1-times more in the UK per annum (ratio mean 3·7 [SD 0·8]). This difference was associated with the higher success of the MDR clone ST131-C2 (pseudo-R2 69·1%). A non-neutral Wright-Fisher model replicated the observed expansion of non-MDR and MDR sequence types under higher DDD regimes. INTERPRETATION: Our study indicates that resistance profiles of contemporaneously successful clones can vary substantially, warranting caution in the interpretation of correlations between aggregate measures of resistance and antibiotic usage. Our study further suggests that in countries with low-to-moderate use of antibiotics, such as the UK and Norway, the extent of non-penicillin β-lactam use modulates rather than determines the success of widely disseminated MDR ESBL-carrying E coli clones. Detailed understanding of underlying causal drivers of success is important for improved control of resistant pathogens.FUNDING: Trond Mohn Foundation, Marie Skłodowska-Curie Actions, European Research Council, Royal Society, and Wellcome Trust.</p