Across the pond: alternative ways of obtaining scholarly articles and the impact on traditional publishing models, from a UK/European perspective

This column examines the growth and impact of open access (OA) with emphasis on a UK/European perspective. It considers the various colors of OA, the impact on authors, institutions, and funders, and speculates on the future of traditional academic publishing. The author considers the pros and cons of a variety of OA methods--including the so-called ‘guerrilla OA’ services and sites-- and discusses the current mandates in place for the UK’s upcoming Research Excellence Framework exercise, which will report back on the research outputs produced in universities between 2014-2020

Developing a multi-methodological approach to hospital operating theatre scheduling

Operating theatres and surgeons are among the most expensive resources in any hospital, so it is vital that they are used efficiently. Due to the complexity of the challenges involved in theatre scheduling we split the problem into levels and address the tactical and day-to-day scheduling problems.Cognitive mapping is used to identify the important factors to consider in theatre scheduling and their interactions. This allows development and testing of our understanding with hospital staff, ensuring that the aspects of theatre scheduling they consider important are included in the quantitative modelling.At the tactical level, our model assists hospitals in creating new theatre timetables, which take account of reducing the maximum number of beds required, surgeons’ preferences, surgeons’ availability, variations in types of theatre and their suitability for different types of surgery, limited equipment availability and varying the length of the cycle over which the timetable is repeated. The weightings given to each of these factors can be varied allowing exploration of possible timetables.At the day-to-day scheduling level we focus on the advanced booking of individual patients for surgery. Using simulation a range of algorithms for booking patients are explored, with the algorithms derived from a mixture of scheduling literature and ideas from hospital staff. The most significant result is that more efficient schedules can be achieved by delaying scheduling as close to the time of surgery as possible, however, this must be balanced with the need to give patients adequate warning to make arrangements to attend hospital for their surgery.The different stages of this project present different challenges and constraints, therefore requiring different methodologies. As a whole this thesis demonstrates that a range of methodologies can be applied to different stages of a problem to develop better solutions

Medicalization and representations of smoking in public discourse and images.

An approach to smoking through an analysis of its representations, grounded in the medicalization literature, highlights the inadequacies of a narrow medical perspective and some of its negative implications. This does not require that we abandon the medical discourse, but stresses the importance of setting it in a wider representational context. Drawing on the work of Saussure, Barthes, Eco and Foucault, the author constructs a theory of interaction amongst representations suited to both discourse and images. To investigate the medicalization of smoking, four empirical studies are reported which include quantitative and qualitative approaches to press reporting at both macro-and micro-levels, cigarette advertising and packaging. There have been medical representations of smoking since the introduction of tobacco into Britain. However, a thematic analysis of tobacco-related reporting in the Times newspaper (1946-1995) found that these representations have expanded and diversified, becoming increasingly linked to other representations (e.g. financial) and generating new themes (e.g. discrimination, litigation). Medical representations, however, are contested and subject to subversion by alternative representations, including libertarian and alternative medical constructions of smoking. These processes are investigated in a detailed structural and rhetorical analysis of a contemporary newspaper article, together with related correspondence and cartoons. Quantitative and qualitative analyses of 754 UK cigarette advertisements from four national newspapers (1946-1995) identified an increase in medical and packaging-related representations of smoking and a decrease in financial representations, representations of the act of smoking and of cigarettes as social currency. The final, questionnaire, study (with 60 participants) found, among other things, a clear and consensually-held system of health-related signification in contemporary UK cigarette packaging in ratings of packets. The thesis concludes with a discussion of the implications of medicalization for smoking-related policy and for the smoker, and of smoking for the medicalization literature

A multi-hit hypothesis for an APOE4-dependent pathophysiological state

The APOE gene encoding the Apolipoprotein E protein is the single most significant genetic risk factor for late-onset Alzheimer's disease. The APOE4 genotype confers a significantly increased risk relative to the other two common genotypes APOE3 and APOE2. Intriguingly, APOE4 has been associated with neuropathological and cognitive deficits in the absence of Alzheimer's disease-related amyloid or tau pathology. Here, we review the extensive literature surrounding the impact of APOE genotype on central nervous system dysfunction, focussing on preclinical model systems and comparison of APOE3 and APOE4, given the low global prevalence of APOE2. A multi-hit hypothesis is proposed to explain how APOE4 shifts cerebral physiology towards pathophysiology through interconnected hits. These hits include the following: neurodegeneration, neurovascular dysfunction, neuroinflammation, oxidative stress, endosomal trafficking impairments, lipid and cellular metabolism disruption, impaired calcium homeostasis and altered transcriptional regulation. The hits, individually and in combination, leave the APOE4 brain in a vulnerable state where further cumulative insults will exacerbate degeneration and lead to cognitive deficits in the absence of Alzheimer's disease pathology and also a state in which such pathology may more easily take hold. We conclude that current evidence supports an APOE4 multi-hit hypothesis, which contributes to an APOE4 pathophysiological state. We highlight key areas where further study is required to elucidate the complex interplay between these individual mechanisms and downstream consequences, helping to frame the current landscape of existing APOE-centric literature

The pregnant man: race, difference and subjectivity in Alan Paton’s Kalahari writing

In South African imaginative writing and scholarly research, there is currently an extensive and wide-ranging interest in the ‘Bushman’, either as a tragic figure of colonial history, as a contested site of misrepresentation, or even as an exemplary model of environmental consciousness. Writing and research about ‘Bushmen’ has not only become pervasive in the academy, but also a site of controversy and theoretical contestation. It is in this context that this paper investigates the meaning and significance of ‘Bushmen’ for Alan Paton, one of South Africa’s most well-known writers. Paton’s writing is not usually associated with ‘Bushman’ studies, yet this article shows that the ‘Bushman’ became a highly charged and ambivalent figure in his imagination. Paton’s problematic ideas are contextualised more carefully by looking at the broader context of South African letters. The article initially analyses Paton’s representation of ‘Bushmen’ in his Lost City of the Kalahari travel narrative (1956, published in 2005. Pietermaritzburg: KZN Press), and also discusses unpublished archival photographs. A study of the figure of the ‘Bushman’ throughout the entire corpus of his writing, ranging from early journalism to late autobiography, allows us to trace the shift of his views, enabling us to reflect not only on Paton’s thinking about racial otherness, but also gauge the extent to which his encounter with the Kalahari Bushmen destabilised his sense of self, finally also preventing the publication of the travelogueDepartment of HE and Training approved lis

Common HLA Alleles Associated with Health, but Not with Facial Attractiveness

Three adaptive hypotheses have been proposed to explain the link between the human leucocyte antigen (HLA) genes, health measures and facial attractiveness: inbreeding avoidance, heterozygote advantage and frequency-dependent selection. This paper reports findings that support a new hypothesis relating HLA to health. We suggest a new method to quantify the level of heterozygosity. HLA heterozygosity did not significantly predict health measures in women, but allele frequency did. Women with more common HLA alleles reported fewer cold and flu bouts per year, fewer illnesses in the previous year and rated themselves healthier than women with rare alleles. To our knowledge, this is the first study to show a positive correlation between HLA allele frequency and general health measures. We propose that certain common HLA alleles confer resistance to prevalent pathogens. Nevertheless, neither HLA heterozygosity nor allele frequency significantly predicted how healthy or attractive men rated the female volunteers. Three non-mutually exclusive explanations are put forward to explain this finding

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice