Developing a Culture of Publication: a joint enterprise writing retreat

Purpose: Many students irrespective of level of study produce excellent course work which, if given support and encouragement could clearly be of a publishable standard. Academic staff are expected to produce quality publications meeting peer review standards although they may be relatively novice authors. All are engaged in some aspects of academic writing practices but not as frequently involved in co-production of publications emanating from student work. This activity is still at the margins of much of the student experience. Design/methodology: Mindful of these issues, we designed and offered a writing programme including a writing retreat. This brought together undergraduate and postgraduate students from a range of applied disciplines (health and art, design and architecture) and their supervisors with the aim of co-producing publications and participating in a community of scholarly practice. The project was delivered over nine months. It involved four days ‘compulsory’ attendance and included a preparatory workshop, a two day off campus writing retreat and a dissemination event. Student and supervisors applied to participate as a team. Kirkpatrick’s (2006) four-stage classic model: reaction, learning, changes in behaviour and real world results was used as a framework for the educational evaluation. Key findings organised thematically were: Supervisor-supervisee relationships; space and time; building confidence enabling successful writing and publication. Originality/Value: This paper will provide an overview of the design, content and approaches used for successful delivery of this innovative project. It will draw on examples that illustrate the different types of joint enterprise that emerged, illuminate experiences of co-production and co-authorship along with recommendations for future ventures

子宮頸部及び内膜における aromatase の局在と周期性変化

Objectives: To determine the role of maternal CYP1A1, GSTT1, and GSTM1 metabolic gene polymorphisms in modulating the association between pregnancy smoking exposure and fetal growth restriction. Study design: A case-control study was conducted to investigate if the association of pregnancy smoking and birth outcome was modulated by maternal gene polymorphisms. A total of 90 mothers with an IUGR baby (cases) and 180 mothers without IUGR (controls) were enrolled. Results: Almost half of smokers who carried a CYP1A1 variant (51.3%), GSTT1 null (43.6%), or GSTM1 null genotypes (64.1%) delivered a baby with IUGR. Smokers with the variant CYP1A1 "aa" genotype had babies with lower mean birthweight than non-smokers with the same genotype (p = 0.004). An interaction test showed increased prevalence of IUGR in smokers with the CYP1A1 (Aa/aa) variant (adjusted OR, 1.9; 95% CI, 1.4-5.5, p = 0.01), or with the GSTT1 null (AOR, 1.5; 1.1-3.1, p = 0.001), or GSTM1 null genotypes (AOR, 1.5; 1.2-3.7, p = 0.001). Conclusions: Risk of fetal growth restriction in mothers who smoked during pregnancy was modulated by maternal metabolic gene polymorphisms. The genetic control of the conversion of toxic metabolites of tobacco smoke to less damaging substances is important for maternal and fetal health. (C) 2008 Elsevier Ireland Ltd. All rights reserved

A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases

In high-grade serous ovarian cancer (HGSOC), higher densities of both B cells and the CD8 + T-cell infiltrate were associated with a better prognosis. However, the precise role of B cells in the antitumor response remains unknown. As peritoneal metastases are often responsible for relapse, our aim was to characterize the role of B cells in the antitumor immune response in HGSOC metastases. Unmatched pre and post-chemotherapy HGSOC metastases were studied. B-cell localization was assessed by immunostaining. Their cytokines and chemokines were measured by a multiplex assay, and their phenotype was assessed by flow cytometry. Further in vitro and in vivo assays highlighted the role of B cells and plasma cell IgGs in the development of cytotoxic responses and dendritic cell activation. B cells mainly infiltrated lymphoid structures in the stroma of HGSOC metastases. There was a strong B-cell memory response directed at a restricted repertoire of antigens and production of tumor-specific IgGs by plasma cells. These responses were enhanced by chemotherapy. Interestingly, transcript levels of CD20 correlated with markers of immune cytolytic responses and immune complexes with tumor-derived IgGs stimulated the expression of the costimulatory molecule CD86 on antigen-presenting cells. A positive role for B cells in the antitumor response was also supported by B-cell depletion in a syngeneic mouse model of peritoneal metastasis. Our data showed that B cells infiltrating HGSOC omental metastases support the development of an antitumor response. Clin Cancer Res; 1-13. ©2016 AACR

Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma

This research was funded by Swiss Cancer League (BIL KLS-2883-02-2012), the European Research Council (ERC322566), Cancer Research UK (A16354), and Barts and The London Charity (467/1307)

Lambs with Scrapie Susceptible Genotypes Have Higher Postnatal Survival

BACKGROUND: Prion protein (PrP) alleles associated with scrapie susceptibility persist in many sheep populations even with high frequencies despite centuries of selection against them. This suggests that scrapie susceptibility alleles have a pleiotropic effect or are associated with fitness or other traits that have been subject to selection. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped all lambs in two scrapie-free Scottish Blackface sheep flocks for polymorphisms at codons 136, 154 and 171 of the PrP gene. We tested potential associations of the PrP genotype with lamb viability at birth and postnatal survival using a complementary log-log link function and a Weibull proportional hazard model, respectively. Here we show there is an association between PrP genotype, as defined by polymorphisms at codons 154 ad 171, and postnatal lamb survival in the absence of scrapie. Sheep carrying the wild-type ARQ allele have higher postnatal survival rates than sheep carrying the more scrapie-resistant alleles (ARR or AHQ). CONCLUSION: The PrP genotypes associated with higher susceptibility to scrapie are associated with improved postnatal survival in the absence of the disease. This association helps to explain the existence, and in many instances the high frequency, of the ARQ allele in sheep populations

A Risk Score for Predicting Multiple Sclerosis

Multiple sclerosis (MS) develops as a result of environmental influences on the genetically susceptible. Siblings of people with MS have an increased risk of both MS and demonstrating asymptomatic changes in keeping with MS. We set out to develop an MS risk score integrating both genetic and environmental risk factors. We used this score to identify siblings at extremes of MS risk and attempted to validate the score using brain MRI.78 probands with MS, 121 of their unaffected siblings and 103 healthy controls were studied. Personal history was taken, and serological and genetic analysis using the illumina immunochip was performed. Odds ratios for MS associated with each risk factor were derived from existing literature, and the log values of the odds ratios from each of the risk factors were combined in an additive model to provide an overall score. Scores were initially calculated using log odds ratio from the HLA-DRB1*1501 allele only, secondly using data from all MS-associated SNPs identified in the 2011 GWAS. Subjects with extreme risk scores underwent validation studies. MRI was performed on selected individuals.There was a significant difference in the both risk scores between people with MS, their unaffected siblings and healthy controls (p<0.0005). Unaffected siblings had a risk score intermediate to people with MS and controls (p<0.0005). The best performing risk score generated an AUC of 0.82 (95%CI 0.75–0.88).The risk score demonstrates an AUC on the threshold for clinical utility. Our score enables the identification of a high-risk sibling group to inform pre-symptomatic longitudinal studies

Parasite Transmission in Social Interacting Hosts: Monogenean Epidemics in Guppies

Background: Infection incidence increases with the average number of contacts between susceptible and infected individuals. Contact rates are normally assumed to increase linearly with host density. However, social species seek out each other at low density and saturate their contact rates at high densities. Although predicting epidemic behaviour requires knowing how contact rates scale with host density, few empirical studies have investigated the effect of host density. Also, most theory assumes each host has an equal probability of transmitting parasites, even though individual parasite load and infection duration can vary. To our knowledge, the relative importance of characteristics of the primary infected host vs. the susceptible population has never been tested experimentally. Methodology/Principal Findings: Here, we examine epidemics using a common ectoparasite, Gyrodactylus turnbulli infecting its guppy host (Poecilia reticulata). Hosts were maintained at different densities (3, 6, 12 and 24 fish in 40 L aquaria), and we monitored gyrodactylids both at a population and individual host level. Although parasite population size increased with host density, the probability of an epidemic did not. Epidemics were more likely when the primary infected fish had a high mean intensity and duration of infection. Epidemics only occurred if the primary infected host experienced more than 23 worm days. Female guppies contracted infections sooner than males, probably because females have a higher propensity for shoaling. Conclusions/Significance: These findings suggest that in social hosts like guppies, the frequency of social contact largely governs disease epidemics independent of host density

Investigating β-catenin and the Norrin signalling pathway in FEVR

Familial exudative vitreoretinopathy (FEVR) is a rare inherited blindness disorder characterised by peripheral retinal avascularity. FEVR has a highly variable clinical presentation with a phenotypic spectrum ranging from asymptomatic to blindness at birth. The Norrin/β-catenin pathway plays a key role in angiogenesis and retinal vascular development and is implicated in vascular retinopathies including FEVR. This study investigated the functional impact of two FEVR mutations affecting the C-terminal domain (CTD) of β-catenin, p.(Arg710Cys) and p.(His720*). Results from a range of in-vitro cell-based assays questioned the pathogenicity of the p.(Arg710Cys) missense variant. However, TOPflash assay results indicated that the p.(His720*) nonsense variant causes transcription defects and localization studies showed these were not due to defects in nuclear translocation, suggesting β-catenin’s CTD may have key functional roles in transcription. This work led to the development of a CRISPR-Cas9 mouse model (CTNNB1-H720X-EM1-B6) to further explore the pathogenic effects of truncated β-catenin in-vivo. Also in this study, a high-throughput RNAi screen was developed and trialled to characterise components of the Norrin/β-catenin pathway. A kinase screen identified both expected and potentially novel pathway components including an uncharacterised protein, Wnt/β-catenin related hits (PRKAR2B, TRIB2, RAF1 and RIOK3), hits with roles in angiogenesis and Wnt signalling (FLT1, VEGF Receptor 1) and a hit linked to the FEVR phenotype of retinal peripheral avascularity (IKBKG). Altogether, these findings are expected to enhance our understanding of the complex Norrin/β-catenin pathway. The H720X mouse model will enable investigation of the transcriptional and binding profile of variant β-catenin. Newly discovered components will shed light to the molecular mechanisms of Norrin signalling and FEVR, providing future opportunities for new therapeutic approaches