Lessons from Love-Locks: The archaeology of a contemporary assemblage

This document is the Accepted Manuscript version. The final, definitive version of this paper has been published in Journal of Material Culture, November 2017, published by SAGE Publishing, All rights reserved.Loss of context is a challenge, if not the bane, of the ritual archaeologist’s craft. Those who research ritual frequently encounter difficulties in the interpretation of its often tantalisingly incomplete material record. Careful analysis of material remains may afford us glimpses into past ritual activity, but our often vast chronological separation from the ritual practitioners themselves prevent us from seeing the whole picture. The archaeologist engaging with structured deposits, for instance, is often forced to study ritual assemblages post-accumulation. Many nuances of its formation, therefore, may be lost in interpretation. This paper considers what insights an archaeologist could gain into the place, people, pace, and purpose of deposition by recording an accumulation of structured deposits during its formation, rather than after. To answer this, the paper will focus on a contemporary depositional practice: the love-lock. This custom involves the inscribing of names/initials onto a padlock, its attachment to a bridge or other public structure, and the deposition of the corresponding key into the water below; a ritual often enacted by a couple as a statement of their romantic commitment. Drawing on empirical data from a three-year diachronic site-specific investigation into a love-lock bridge in Manchester, UK, the author demonstrates the value of contemporary archaeology in engaging with the often enigmatic material culture of ritual accumulations.Peer reviewe

Novel inflammatory cell infiltration scoring system to investigate healthy and footrot affected ovine interdigital skin

Ovine footrot is a degenerative disease of sheep feet leading to the separation of hoofhorn from the underlying skin and lameness. This study quantitatively examined histological features of the ovine interdigital skin as well as their relationship with pro-inflammatory cytokine (IL-1_) and virulent Dichelobacter nodosus in footrot. From 55 healthy and 30 footrot ovine feet, parallel biopsies (one fixed for histology) were collected post-slaughter and analysed for lesions and histopathological analysis using haematoxylin and eosin and Periodic Acid-Schiff. Histological lesions were similar in both conditions while inflammatory scores mirror IL-1_ expression levels. Increased inflammatory score corresponded with high virulent D. nodosus load and was significant (

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Predicting outcomes after blunt chest wall trauma: development and external validation of a new prognostic model. Crit Care 2014;18:R98

in press). Predicting outcomes after blunt chest wall trauma: development and external validation of a new prognostic model. Critical Care, 18(R98) http://dx.doi.org/doi:10.1186/cc13873 _____________________________________________________________ This article is brought to you by Swansea University. Any person downloading material is agreeing to abide by the terms of the repository licence. Authors are personally responsible for adhering to publisher restrictions or conditions. When uploading content they are required to comply with their publisher agreement and the SHERPA RoMEO database to judge whether or not it is copyright safe to add this version of the paper to this repository. Abstract Introduction: Blunt chest wall trauma accounts for over 15% of all trauma admissions to Emergency Departments worldwide. Reported mortality rates vary between 4 and 60%. Management of this patient group is challenging as a result of the delayed on-set of complications. The aim of this study was to develop and validate a prognostic model that can be used to assist in the management of blunt chest wall trauma. Methods: There were two distinct phases to the overall study; the development and the validation phases. In the first study phase, the prognostic model was developed through the retrospective analysis of all blunt chest wall trauma patients (n = 274) presenting to the Emergency Department of a regional trauma centre in Wales (2009 to 2011). Multivariable logistic regression was used to develop the model and identify the significant predictors for the development of complications. The model's accuracy and predictive capabilities were assessed. In the second study phase, external validation of the model was completed in a multi-centre prospective study (n = 237) in 2012. The model's accuracy and predictive capabilities were re-assessed for the validation sample. A risk score was developed for use in the clinical setting. Results: Significant predictors of the development of complications were age, number of rib fractures, chronic lung disease, use of pre-injury anticoagulants and oxygen saturation levels. The final model demonstrated an excellent c-index of 0.96 (95% confidence intervals: 0.93 to 0.98). Conclusions: In our two phase study, we have developed and validated a prognostic model that can be used to assist in the management of blunt chest wall trauma patients. The final risk score provides the clinician with the probability of the development of complications for each individual patient

Protocol for a population-based Ankylosing Spondylitis (PAS) cohort in Wales

<p>Abstract</p> <p>Background</p> <p>To develop a population-based cohort of people with ankylosing spondylitis (AS) in Wales using (1) secondary care clinical datasets, (2) patient-derived questionnaire data and (3) routinely-collected information in order to examine disease history and the health economic cost of AS.</p> <p>Methods</p> <p>This data model will include and link (1) secondary care clinician datasets (i.e. electronic patient notes from the rheumatologist) (2) patient completed questionnaires (giving information on disease activity, medication, function, quality of life, work limitations and health service utilisation) and (3) a broad range of routinely collected data (including; GP records, in-patient hospital admission data, emergency department data, laboratory/pathology data and social services databases). The protocol involves the use of a unique and powerful data linkage system which allows datasets to be interlinked and to complement each other.</p> <p>Discussion</p> <p>This cohort can integrate patient supplied, primary and secondary care data into a unified data model. This can be used to study a range of issues such as; the true economic costs to the health care system and the patient, factors associated with the development of severe disease, long term adverse events of new and existing medication and to understand the disease history of this condition. It will benefit patients, clinicians and health care managers. This study forms a pilot project for the use of routine data/patient data linked cohorts for other chronic conditions.</p

Evaluating the application of Pareto navigation guided automated radiotherapy treatment planning to prostate cancer

Background and purpose Current automated planning methods do not allow for the intuitive exploration of clinical trade-offs during calibration. Recently a novel automated planning solution, which is calibrated using Pareto navigation principles, has been developed to address this issue. The purpose of this work was to clinically validate the solution for prostate cancer patients with and without elective nodal irradiation. Materials and methods For 40 randomly selected patients (20 prostate and seminal vesicles (PSV) and 20 prostate and pelvic nodes (PPN)) automatically generated volumetric modulated arc therapy plans (VMATAuto) were compared against plans created by expert dosimetrists under clinical conditions (VMATClinical) and no time pressures (VMATIdeal). Plans were compared through quantitative comparison of dosimetric parameters and blind review by an oncologist. Results Upon blind review 39/40 and 33/40 VMATAuto plans were considered preferable or equal to VMATClinical and VMATIdeal respectively, with all deemed clinically acceptable. Dosimetrically, VMATAuto, VMATClinical and VMATIdeal were similar, with observed differences generally of low clinical significance. Compared to VMATClinical, VMATAuto reduced hands-on planning time by 94% and 79% for PSV and PPN respectively. Total planning time was significantly reduced from 22.2 mins to 14.0 mins for PSV, with no significant reduction observed for PPN. Conclusions A novel automated planning solution has been evaluated, whose Pareto navigation based calibration enabled clinical decision-making on trade-off balancing to be intuitively incorporated into automated protocols. It was successfully applied to two sites of differing complexity and robustly generated high quality plans in an efficient manner

Treatment of hidradenitis suppurativa evaluation study: the THESEUS prospective cohort study

Background Hidradenitis suppurativa is a chronic inflammatory skin disease characterised by recurrent inflammatory lesions and skin tunnels in flexural sites such as the axilla. Deroofing of skin tunnels and laser treatment are standard hidradenitis suppurativa interventions in some countries but not yet introduced in the United Kingdom. Objective To understand current hidradenitis suppurativa management pathways and what influences treatment choices to inform the design of future randomised controlled trials. Design Prospective 12-month observational cohort study, including five treatment options, with nested qualitative interviews and an end-of-study consensus workshop. Setting Ten United Kingdom hospitals with recruitment led by dermatology and plastic surgery departments. Participants Adults with active hidradenitis suppurativa of any severity not adequately controlled by current treatment. Interventions Oral doxycycline 200 mg once daily; oral clindamycin and rifampicin, both 300 mg twice daily for 10 weeks initially; laser treatment targeting the hair follicle (neodymium-doped yttrium aluminium garnet or alexandrite); deroofing; and conventional surgery. Main outcome measures Primary outcome was the proportion of participants who are eligible, and hypothetically willing, to use the different treatment options. Secondary outcomes included proportion of participants choosing each of the study interventions, with reasons for their choices; proportion of participants who switched treatments; treatment fidelity; loss to follow-up rates over 12 months; and efficacy outcome estimates to inform outcome measure instrument responsiveness. Results Between February 2020 and July 2021, 151 participants were recruited, with two pauses due to the COVID-19 pandemic. Follow-up rates were 89% and 83% after 3 and 6 months, decreasing to 70% and 44% at 9 and 12 months, respectively, because pandemic recruitment delays prevented all participants reaching their final review. Baseline demographics included an average age of 36 years, 81% female, 20% black, Asian or Caribbean, 64% current or ex-smokers and 86% with a raised body mass index. Some 69% had moderate disease, 19% severe disease and 13% mild disease. Regarding the study’s primary outcome, laser treatment was the intervention with the highest proportion (69%) of participants who were eligible and hypothetically willing to receive treatment, followed by deroofing (58%), conventional surgery (54%), the combination of oral clindamycin and rifampicin (44%) and doxycycline (37%). Considering participant willingness in isolation, laser was ranked first choice by the greatest proportion (41%) of participants. The cohort study and qualitative study demonstrated that participant willingness to receive treatment was strongly influenced by their clinician. Fidelity to oral doxycycline was only 52% after 3 months due to lack of effectiveness, participant preference and adverse effects. Delays receiving procedural interventions were common, with only 43% and 26% of participants commencing laser therapy and deroofing, respectively, after 3 months. Treatment switching was uncommon and there were no serious adverse events. Daily pain score text messages were initiated in 110 participants. Daily responses reduced over time with greatest concordance during the first 14 days

The effects of exercise-induced muscle damage on endurance performance

It is well documented that engaging in resistance exercise can lead to further improvements in endurance performance. Whilst, not fully understood, it is speculated that increased motor unit recruitment, improved muscle coordination and enhanced utilisation of stored elastic energy after resistance-based exercise improves exercise economy. Nevertheless, while prolonged exposure to resistance training improves endurance performance in the long-term, a consequence of such training when unaccustomed is the appearance of exercise-induced muscle damage (EIMD). Exercise-induced muscle damage is well known to affect athletic performance requiring muscular strength and power; however, its effects on markers of endurance exercise are unclear. Therefore, the aim of this thesis was to investigate the effects of EIMD on endurance performance, with an emphasis on the physiological (oxygen uptake; , minute ventilation; ), metabolic (blood lactate; [La]), perceptual (rating of perceived exertion; RPE) and kinematic (stride length; SL, stride frequency; SF) responses during sub-maximal endurance exercise

Treatment of hidradenitis suppurativa evaluation study (THESEUS): a prospective cohort study

Background Hidradenitis suppurativa (HS) is a chronic, painful disease affecting flexures and other skin regions, producing nodules, abscesses and skin tunnels. Laser treatment targeting hair follicles and deroofing of skin tunnels are standard HS interventions in some countries but rarely offered in the UK. Objectives To describe current UK HS management pathways and influencing factors to inform the design of future randomised controlled trials (RCTs). Methods THESEUS was a non-randomised 12-month prospective cohort study set in 10 UK hospitals offering five interventions: oral doxycycline 200mg daily; oral clindamycin and rifampicin both 300mg twice daily for 10 weeks, extended for longer in some cases; laser treatment targeting hair follicles; deroofing, and conventional surgery. Primary outcome was the combination of clinician-assessed eligibility and participant hypothetical willingness to receive each intervention. Secondary outcomes: proportion of participants selecting each intervention as their final treatment option; proportion who switch treatments; treatment fidelity, and attrition rates. THESEUS was prospectively registered on ISRCTN Registry: ISRCTN69985145. Results The recruitment target of 150 participants was met after 18 months, in July 2021, with two pauses due to the Covid-19 pandemic. Baseline demographics reflected the HS secondary care population: average age 36 years, 81% female, 20% non-white, 64% current or ex-smokers, 86% BMI≥25, 68% moderate disease, 19% severe, and 13% mild disease. Laser was the intervention with the highest proportion (69%) of participants eligible and willing to receive treatment, then deroofing (58%), conventional surgery (54%), clindamycin and rifampicin (44%), and doxycycline (37%). Laser was ranked first choice by the greatest proportion of participants (41%). Attrition rates were 11% and 17% after three and six months respectively. Concordance with doxycycline was 52% after three months due to lack of efficacy, participant choice and adverse effects. Delays with procedural interventions were common, with only 43% and 26% of participants starting laser and deroofing respectively after three months. Uptake of conventional surgery was too small to characterise the intervention. Switching treatment was uncommon and there were no serious adverse events. Conclusions THESEUS established laser treatment and deroofing for HS in the UK and demonstrated their popularity with patients and clinicians for future RCTs