A Note on Ted Hughes and Jonathan Swift

Ted Hughes, three months before he died, when he had completed the huge project that became Shakespeare and the Goddess of Complete Being (1992) and the two long original essays in the collected prose of Winter Pollen (1994), complained that he had spent too much time writing prose. He even believed that this had somehow destroyed his immune system (Letters 719). He wrote that, avoiding the issue of engaging with the material in what became Birthday Letters, he ‘took refuge in prose’ (ibid). Certainly his major poetry collections were behind him (with River in 1983). He described his late absorption in prose with a reference to an image from an iconic, not to say mythologised, moment from his days as a Cambridge undergraduate: ‘5or 6 years nothing but prose – nothing but burning the foxes’ (ibid). In his famous record of a dream he was writing his weekly essay on the English course, this time on Samuel Jonson, and a fox had appeared with burnt paws which he planted on the page and said ‘You are destroying us’ (see Winter Pollen pp. 8-9). Hughes switched, as was actually not uncommon amongst English students, to Archaeology and Anthropology for his final year

Young teenagers' experiences of domestic abuse

This article reports on the first findings from the Boys to Men Research Project. In total, 1143 pupils aged 1314 years completed a questionnaire to assess their experiences of domestic abuse as victims, witnesses and perpetrators. Overall, 45% of pupils who had been in a dating relationship reported having been victimised, 25% having perpetrated it, with the only difference in rates of victimisation and perpetration between boys and girls being in relation to sexual victimisation. Of the whole sample, 34% reported having witnessed it in their own family. There was a relationship between victimisation and perpetration with the vast majority of perpetrators (92%) also reporting experiencing abuse from a boyfriend/girlfriend. There was also a relationship between experiencing abuse and help seeking from adults, with those who have been victimised less likely to say they would seek help if they were hit by a partner than those who had yet to experience any abuse. The relationship between help seeking and experiences of abuse is further complicated by gender, with girls twice as likely to seek help than boys, but with girls who have previously hit a partner among the most reticent group. The paper concludes with highlighting the implications of these findings for those undertaking preventative work in schools

Using SciVal responsibly: a guide to interpretation and good practice

This guide is designed to help those who use SciVal to source and apply bibliometrics in academic institutions. It was originally devised in February 2018 by Dr Ian Rowlands of King’s College London as a guide for his university, which makes SciVal widely available to its staff. King’s does this because it believes that bibliometric data are best used in context by specialists in the field. A small group of LISBibliometrics committee members reviewed and revised the King’s guide to make it more applicable to a wider audience. SciVal is a continually updated source and so feedback is always welcome at [email protected]. LIS-Bibliometrics is keen that bibliometric data should be used carefully and responsibly and this requires an understanding of the strengths and limitations of the indicators that SciVal publishes. The purpose of this Guide is to help researchers and professional services staff to make the most meaningful use of SciVal. It includes some important `inside track’ insights and practical tips that may not be found elsewhere. The scope and coverage limitations of SciVal are fairly widely understood and serve as a reminder that these metrics are not appropriate in fields where scholarly communication takes place mainly outside of the journals and conference literature. This is one of the many judgment calls that need to be made when putting bibliometric data into their proper context. One of the most useful features of SciVal is the ability to drill down in detail using various filters. This allows a user to define a set of publications accurately, but that may mean generating top level measures that are based on small samples with considerable variance. Bibliometrics distributions are often highly skewed, where even apparently simple concepts like the `average’ can be problematic. So one objective of this Guide is to set out some advice on sample sizes and broad confidence intervals, to avoid over-interpreting the headline data. Bibliometric indicators should always be used in combination, not in isolation, because each can only offer partial insights. They should also be used in a `variable geometry’ along with other quantitative and qualitative indicators, including expert judgments and non-publication metrics, such as grants or awards, to flesh out the picture

High potency of lipid conjugated TLR7 agonist requires nanoparticulate or liposomal formulation

Conjugation of small molecule agonists of Toll-like receptor 7 (TLR7) to proteins, lipids, or polymers is known to modulate potency, and the physical form or formulation of these conjugates is likely to have a major effect on their immunostimulatory activity. Here, we studied the effect of formulation on potency of a 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE) conjugated TLR7 agonist (DOPE-TLR7a) alongside assessing physical form using Dynamic Light Scattering (DLS), Nanosight Particle Tracking (NTA) analysis and Small Angle X-ray Scattering (SAXS). A very high potency of DOPE-TLR7a conjugate (EC50 around 9 nM) was observed either when prepared by direct dilution from DMSO or when formulated into 400-700 nm large multilamella liposomes containing dimethyldioctadecylammonium bromide salt (DDA) and DOPE. When prepared by dissolution in DMSO followed by dilution in aqueous culture medium, 93 ± 5 nm nanoparticles were formed. Without dilution from solution in DMSO, no nanoparticles were observed, and no immunostimulatory activity could be detected without this formulation step. SAXS analysis of the conjugate after DMSO dissolution/water dilution revealed a lamellar order with a layer spacing of 68.7 Å, which correlates with arrangement in groups of 3 bilayers. The addition of another immunostimulatory glycolipid, trehalose-6,6-dibehenate (TDB), to DOPE:DDA liposomes gave no further increase in immunostimulatory activity beyond that provided by incorporating DOPE-TLR7a. Given the importance of nanoparticle or liposomal formulation for activity, we conclude a major mechanism for increase in potency when TLR7 agonists are conjugated to macromolecules is through alteration of physical form

Primary Sources on Copyright revisited: a copyright history webinar on Papal Privileges and the Stationers' Register

This working paper presents an edited transcript of a copyright history webinar held on 15 December 2021, marking 15 years since the conception of the Primary Sources on Copyright (1450-1900) 1 digital archive. Giles Bergel (University of Oxford) and Ian Gadd (Bath Spa University) introduce Stationers’ Register Online (SRO)2 – a new resource that digitises the entries for the literary, musical and artistic works made in the Registers of the Stationers’ Company of London3 between 1557 and 1640. Jane Ginsburg (Columbia Law School) presents a new section on Vatican sources which she (and her team of Latinists) contributed to the Primary Sources digital archive, edited by Lionel Bently (University of Cambridge) and Martin Kretschmer (CREATe, University of Glasgow). The project presentations were followed by a panel discussion, joined by Elena Cooper (CREATe, University of Glasgow) and Neil Netanel (University of California at Los Angeles), two of the national editors of Primary Sources on Copyright. This working paper offers a reference point of wider interest. What should be the ambitions of a primary sources project? Can the history of copyright law be re-written? What is the role of history for policy

Epigenetic scores for the circulating proteome as tools for disease prediction

Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent sample (Generation Scotland; n = 9537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore-disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification

Blood-based epigenome-wide analyses of cognitive abilities

BACKGROUND: Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia. RESULTS: Using blood-based epigenome-wide analyses of general cognitive function, we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in general cognitive function (g). A DNAm predictor explains ~4% of the variance, independently of a polygenic score, in two external cohorts. It also associates with circulating levels of neurology- and inflammation-related proteins, global brain imaging metrics, and regional cortical volumes. CONCLUSIONS: As sample sizes increase, the ability to assess cognitive function from DNAm data may be informative in settings where cognitive testing is unreliable or unavailable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02596-5

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes