‘Slobs and yobs’: representations of youth in the UK newspapers 1st January to 30th June 2005

Many authors have pointed to the ways in which newspapers negatively stereotype young people. This thesis aims to engage with and contribute to this debate through a contemporary discursive analysis of newspaper representations of youth, in The Guardian, The Daily Mail and The Daily Mirror during the period 1(^st) January to 30(^th) June 2005. My aim is to make explicit the discourses, both contemporary and historical, that circulated in the press during this period. It is through such discourses that young people were identified, explained and represented at this juncture. It will be argued that those young people deemed problematic by the press are represented in particular classed ways and understood through a discourse of 'underclass'; by which young people are constructed as victims of their families. Further, in 2005, as in the nineteenth- century, the poor working-class (understood as uncultured/uncivilized) are blamed for societies ills and such a discursive configuration has inevitable consequences and effects for both young people and their families

Nurses\u27 Alumnae Association Bulletin, June 1965

President\u27s Page Officers and Committee Chairmen Financial Report Hospital and School of Nursing Report Student Activities Annual Report Students Activities Annual Report Student Activities Annual Report Jefferson Expansion Program Psychiatric Unit Progress of the Alumnae Association Nightingale Pledge Resume of Alumnae Meetings Nursing Service Staff Association Scholarship Program Sick and Welfare Social Committee Report Bulletin Membership- WHY JOIN? Private Duty Report Annual Giving Report - 1964 PIT Alumnae Day Notes Building Fund Report - 1965 Vital Statistics IN MEMORIAM Class News Affiliated Institutions Notice

Pathogenic <i>NR2F1</i> variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Funder: National Institute of Health Research Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of OphthalmologyPathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system

Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system

Sonic Hedgehog and Notch Signaling Can Cooperate to Regulate Neurogenic Divisions of Neocortical Progenitors

Innate lymphoid cells (ILCs) and innate-like lymphocytes have important roles in immune responses in the context of infection, cancer, and autoimmunity. The factors involved in driving the differentiation and function of these cell types remain to be clearly defined. There are several cellular signaling pathways involved in embryogenesis, which continue to function in adult tissue. In particular, the WNT, NOTCH, and Hedgehog signaling pathways are emerging as regulators of hematopoietic cell development and differentiation. This review discusses the currently known roles of WNT, NOTCH, and Hedgehog signaling in the differentiation and function of ILCs and innate-like lymphocytes

Breeding progress and preparedness for mass‐scale deployment of perennial lignocellulosic biomass crops switchgrass, miscanthus, willow and poplar

UK: The UK‐led miscanthus research and breeding was mainly supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Department for Environment, Food and Rural Affairs (Defra), the BBSRC CSP strategic funding grant BB/CSP1730/1, Innovate UK/BBSRC “MUST” BB/N016149/1, CERES Inc. and Terravesta Ltd. through the GIANT‐LINK project (LK0863). Genomic selection and genomewide association study activities were supported by BBSRC grant BB/K01711X/1, the BBSRC strategic programme grant on Energy Grasses & Bio‐refining BBS/E/W/10963A01. The UK‐led willow R&D work reported here was supported by BBSRC (BBS/E/C/00005199, BBS/E/C/00005201, BB/G016216/1, BB/E006833/1, BB/G00580X/1 and BBS/E/C/000I0410), Defra (NF0424) and the Department of Trade and Industry (DTI) (B/W6/00599/00/00). IT: The Brain Gain Program (Rientro dei cervelli) of the Italian Ministry of Education, University, and Research supports Antoine Harfouche. US: Contributions by Gerald Tuskan to this manuscript were supported by the Center for Bioenergy Innovation, a US Department of Energy Bioenergy Research Center supported by the Office of Biological and Environmental Research in the DOE Office of Science, under contract number DE‐AC05‐00OR22725. Willow breeding efforts at Cornell University have been supported by grants from the US Department of Agriculture National Institute of Food and Agriculture. Contributions by the University of Illinois were supported primarily by the DOE Office of Science; Office of Biological and Environmental Research (BER); grant nos. DE‐SC0006634, DE‐SC0012379 and DE‐SC0018420 (Center for Advanced Bioenergy and Bioproducts Innovation); and the Energy Biosciences Institute. EU: We would like to further acknowledge contributions from the EU projects “OPTIMISC” FP7‐289159 on miscanthus and “WATBIO” FP7‐311929 on poplar and miscanthus as well as “GRACE” H2020‐EU.3.2.6. Bio‐based Industries Joint Technology Initiative (BBI‐JTI) Project ID 745012 on miscanthus.Peer reviewedPostprintPublisher PD

A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant