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Abstract Background Current guidelines for diabetic ketoacidosis (DKA) recommend treatment with normal saline (NS). However, NS, with its high chloride concentrations, may worsen acidosis and contribute to a hyperchloremic metabolic acidosis. Alternatives to NS are balanced crystalloids (e.g. Ringer’s Lactate [RL]) which have chloride concentrations similar to human plasma; therefore, treatment with balanced crystalloids may lead to faster DKA resolution. A recent systematic review and meta-analysis by Catahay et al. (2022) demonstrated the need for more blinded, high-quality trials comparing NS versus RL in the treatment of DKA. Methods We describe a protocol for BRISK-ED (Balanced crystalloids [RInger’s lactate] versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department). Our study is a single-centre, triple-blind, pilot randomized controlled trial (RCT) of adults (≥ 18 years) with DKA presenting to an academic tertiary care ED in London, Canada. Patients with clinical suspicion for DKA will be screened and those found to not meet DKA criteria or have euglycemic DKA will be excluded. We will aim to recruit 52 patients with DKA and will randomize them 1:1 to receive intravenous RL or NS. The primary feasibility outcome will be recruitment rate, and the primary efficacy outcome will be time elapsed from ED presentation to DKA resolution. Secondary outcomes include time to insulin infusion discontinuation, intensive care unit admission, in-hospital death, and major adverse kidney events within 30 days, defined as a composite of: i) death, ii) new renal replacement therapy, or iii) final serum creatinine ≥ 200% baseline at the earliest of hospital discharge or 30 days after ED presentation. Patients, clinicians, and outcome assessors will be blinded to allocation group. We will follow an intention-to-treat analysis. Gehan-Wilcoxon, Mann–Whitney U, or chi-square tests will be used to compare groups as appropriate. Discussion The results of this pilot study will inform the design and feasibility of a full-scale, multicentre RCT to assess fluid choice in adult ED patients with DKA. If proven to demonstrate faster resolution of DKA, administration of balanced crystalloids may replace NS in diabetes treatment guidelines and improve patient and health systems outcomes. Trial registration ClinicalTrials.gov, Registration # NCT04926740; Registered June 15, 2021.

Background Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. Objectives The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers. Design and methods This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)–Hospital Episode Statistics (HES) linked primary–secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals. Result Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (p

Platelet-rich plasma (PRP) is an autologous preparation that has been claimed to improve healing and mechanobiological properties of tendons both in vitro and in vivo. In this sub-study from the PATH-2 (PRP in Achilles Tendon Healing-2) trial, we report the cellular and growth factor content and quality of the Leukocyte-rich PRP (L-PRP) (N = 103) prepared using a standardized commercial preparation method across 19 different UK centers. Baseline whole blood cell counts (red cells, leukocyte and platelets) demonstrated that the two groups were well-matched. L-PRP analysis gave a mean platelet count of 852.6 x 109/L (SD 438.96), a mean leukocyte cell count of 15.13 x 109/L (SD 10.28) and a mean red blood cell count of 0.91 x 1012/L (SD 1.49). The activation status of the L-PRP gave either low or high expression levels of the degranulation marker CD62p before and after ex-vivo platelet activation respectively. TGF-β, VEGF, PDGF, IGF and FGFb mean concentrations were 131.92 ng/ml, 0.98 ng/ml, 55.34 ng/ml, 78.2 ng/ml and 111.0 pg/ml respectively with expected correlations with both platelet and leukocyte counts. While PATH-2 results demonstrated that there was no evidence L-PRP is effective for improving clinical outcomes at 24 weeks after Achilles tendon rupture, our findings support that the majority of L-PRP properties were within the method specification and performance.

Abstract Background Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood–brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets. Methods Global transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target’s natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis. Results Bioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis. Conclusion ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.

Introduction Hepatitis C virus (HCV) is a global public health threat, and novel models of care are required to treat those currently or previously at highest risk of infection, particularly persons who inject drugs (PWID; ever injected), as conventional healthcare models do not have the reach to deliver cure of HCV to disadvantaged, disproportionately affected communities. In Western Europe and Australasia, it is estimated that HCV affects between 0.4% and 1.0% of the regions’ populations, accordingly, it affects between 0.4% and 0.7% of the populations of countries in this study (Scotland, Wales and Australia). Reaching mEthadone users Attending Community pHarmacies with HCV (REACH HCV) will evaluate community pharmacy-based diagnostic outreach and HCV treatment against conventional HCV testing and treatment pathways for clients receiving opioid substitution therapy (OST) in community pharmacies.Methods and analysis REACH HCV is an international multicentre cluster randomised controlled trial with sites in Scotland, Wales and Australia. The sites are community pharmacies which are randomised equally to one of two pathways: the pharmacy intervention pathway or the education-only (control) pathway. Participants are recruited from OST clients in these pharmacies.In the pharmacy intervention pathway, participants receive a rapid point-of-care HCV PCR test in their pharmacy by a study outreach nurse. If positive, direct-acting antivirals (DAAs) are delivered to participants via their pharmacist in line with their OST schedule.In the education-only pathway, pharmacists counsel OST clients on HCV and refer them to the nearest nurse-led clinic or general practitioner offering HCV testing according to standard care protocols. If positive, DAAs are delivered as in the intervention pathway.The primary endpoint for both pathways is sustained viral response at 12 weeks post-treatment . Secondary outcomes are: cost-efficacy by pathway; participants tested by pathway; adherence to therapy by pathway and impact of blood test results on treatment decisions.A statistical analysis plan will be finalised prior to data lock. Analysis will be by intention to treat (ITT) to show superiority. Modified ITT analysis will also be undertaken to explore the steps in the pathways.Ethics and dissemination The trial received ethical favourable opinion from the East of Scotland Research Ethics Committee 2 (19/ES/0025) for UK sites and approval from the Alfred Hospital Ethics Committee (148/19) for Australian sites and complies with principles of Good Clinical Practice. Final results will be presented in peer-reviewed journals and at relevant conferences.Trial registration number ClinicalTrials.gov Registry NCT03935906.Protocol version V.4.0—19 March 2020.

Abstract Background Acute coronary syndrome (ACS) is a common, sometimes difficult to diagnose spectrum of diseases occurring after abrupt reduction in blood flow through a coronary artery. Given the diagnostic challenge, it is sensible for emergency physicians to have an approach to prognosticate patients with possible ACS. Multiple prediction models have been developed to help identify patients at increased risk of adverse outcomes. The HEART score is the first model to be derived, validated, and undergo clinical impact studies in emergency department (ED) patients with possible ACS. Objective To develop a protocol for a prognostic systematic review of the literature evaluating the HEART score as a predictor of major adverse cardiac events (MACE) in patients presenting to the ED with possible ACS. Methods/design This protocol is reported according to the PRISMA-P statement and is registered on PROSPERO. All methodological tools to be used are endorsed by the Cochrane Prognosis Methods Group. Pre-defined eligibility criteria are provided. Multiple strategies will be used to identify potentially relevant studies. Studies will be selected and data extracted using standardised forms based on the CHARMS checklist. The QUIPS tool will be used to assess the risk of bias within individual studies. Outcome measures will include prevalence, risk ratio, and absolute risk reduction for MACE within 6 weeks of ED evaluation, comparing HEART scores 0–3 versus 4–10. HEART score prognostic performance will be evaluated with the concordance (C) statistic (model discrimination), observed to expected events ratio (model calibration), and a decision curve analysis. Reporting biases and methodological, clinical, and statistical heterogeneity will be scrutinised. Unless deemed inappropriate, a meta-analysis and pre-defined subgroup and sensitivity analyses will be performed. Overall judgements about evidence quality and strength of recommendations will be summarised using the GRADE approach. Discussion This review will identify, select, and appraise studies evaluating the prognostic performance of the HEART score, producing results of interest to emergency physicians. These results may encourage shared clinical decision-making in the ED by facilitating risk communication with patients and health care providers. Systematic review registration PROSPERO 2017 CRD42017084400.

Abstract Background One-third of individuals who sustain an acute lateral ankle ligament sprain suffer significant disability due to pain, functional instability, mechanical instability or recurrent sprain after recovery plateaus at 1 to 5 years post injury. The identification of early prognostic factors associated with poor recovery may provide an opportunity for early-targeted intervention and improve outcome. Methods We performed a comprehensive search of AMED, EMBASE, Psych Info, CINAHL, SportDiscus, PubMed, CENTRAL, PEDro, OpenGrey, abstracts and conference proceedings from inception to September 2016. Prospective studies investigating the association between baseline prognostic factors and recovery over time were included. Two independent assessors performed the study selection, data extraction and quality assessment of the studies. A narrative synthesis is presented due to inability to meta-analyse results due to clinical and statistical heterogeneity. Results The search strategy yielded 3396 titles/abstracts after duplicates were removed. Thirty-six full text articles were then assessed, nine of which met the study inclusion criteria. Six were prospective cohorts, and three were secondary analyses of randomised controlled trials. Results are presented for nine studies that presented baseline prognostic factors for recovery after an acute ankle sprain. Age, female gender, swelling, restricted range of motion, limited weight bearing ability, pain (at the medial joint line and on weight-bearing dorsi-flexion at 4 weeks, and pain at rest at 3 months), higher injury severity rating, palpation/stress score, non-inversion mechanism injury, lower self-reported recovery, re-sprain within 3 months, MRI determined number of sprained ligaments, severity and bone bruise were found to be independent predictors of poor recovery. Age was one prognostic factor that demonstrated a consistent association with outcome in three studies, however cautious interpretation is advised. Conclusions The associations between prognostic factors and poor recovery after an acute lateral ankle sprain are largely inconclusive. At present, there is insufficient evidence to recommend any factor as an independent predictor of outcome. There is a need for well-conducted prospective cohort studies with adequate sample size and long-term follow-up to provide robust evidence on prognostic factors of recovery following an acute lateral ankle sprain. Trial registration Prospero registration: CRD42014014471

Abstract Background Endocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer. However, its efficacy is limited by intrinsic and acquired resistance. Here the potential of S100β as a biomarker and inhibition of its signaling network as a therapeutic strategy in endocrine treated patients was investigated. Methods The expression of S100β in tissue and serum was assessed by immunohistochemistry and an enzyme-linked immunosorbent assay, respectively. The S100β signaling network was investigated in cell line models of endocrine resistance by western blot, PCR, immunoprecipitation, and chromatin-immunoprecipitation. Endocrine resistant xenografts and tumor explants from patients with resistant tumors were treated with endocrine therapy in the presence and absence of the p-Src kinase inhibitor, dasatinib. Results Tissue and serum levels of S100β were found to predict poor disease-free survival in endocrine-treated patients (n = 509, HR 2.32, 95% CI is 1.58–3.40, p

Background: Achilles tendon rupture (ATR) has a long healing period, which is challenging for patients and clinicians. Platelet-rich plasma (PRP) is an autologous concentration of platelets thought to improve tendon function recovery. Although preliminary research has indicated positive effects, there is, as yet, no evidence of clinical efficacy from adequately powered robust clinical trials. Objectives: The objectives were to determine the clinical efficacy of PRP in patients with acute ATR using an objective mechanical muscle–tendon function measure and patient-reported outcome measures (PROMs), and to determine which PRP components contribute to its mechanism. Design: This was a multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial (RCT) comparing PRP with placebo. Two embedded substudies investigated the PRP’s quality and composition and its effects on healing tendon tissues. Setting: This trial was set in trauma and orthopaedic surgery departments in 19 NHS hospitals in England and Wales. Participants: Adults with acute ATR presenting within 12 days of injury to be treated non-surgically were eligible. Patients with platelet dysfunction or leg functional deficiency were excluded. Interventions: Participants were randomised 1 : 1 to the PRP injection group or the placebo group (dry needle in the rupture gap) by central computer-based randomisation using minimisation, stratified by centre and age. Main outcome measures: The primary outcome measure was the Limb Symmetry Index (LSI) of work during the heel-rise endurance test at 24 weeks. Secondary outcomes measures, collected at 4, 7, 13 and 24 weeks, were repetitions, maximum heel-rise height, Achilles tendon Total Rupture Score (ATRS), quality of life (as measured using the Short Form questionnaire-12 items version 2), pain and participant goal attainment. Needle biopsies of the affected tendon zone were taken under ultrasound guidance at 6 weeks from 16 participants from one centre. Whole blood was analysed for cell count. PRP was analysed for cell count, platelet activation and growth factor concentration. The primary analysis was intention to treat. Results: A total of 230 participants were randomised: 114 to the PRP group (103 treated) and 116 to the placebo group (all treated). One participant withdrew after randomisation but before the intervention. At 24 weeks, 201 out of 230 participants (87.4%) completed the primary outcome and 216 out of 230 participants (93.9%) completed the PROMs. The treatment groups had similar participant characteristics. At 24 weeks, there was no difference in work LSI (mean difference –3.872; 95% confidence interval –10.454 to 2.710; p = 0.231), ATRS, pain or goal attainment between PRP- and placebo-injected participants. There were no differences between the groups in any PROM at any time point or in complication rates, including re-rupture and deep-vein thrombosis. There was no correlation between work LSI and platelet activation in PRP, or erythrocyte, leucocyte or platelet counts in whole blood or PRP. Biopsies showed similar cellularity and vascularity between groups. Conclusions: This trial design and standardised PRP preparation gives the first robust RCT evidence about PRP’s role in managing ATR, which suggests that PRP offers no patient benefit. Equally robust evidence to investigate PRP application in tendon and soft tissue injuries is required. The 24-month follow-up will be completed in April 2020. Trial registration: Current Controlled Trials ISRCTN54992179. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The trial was supported by the NIHR Biomedical Research Centre, Oxford, and the NIHR Fellowship programme.

Introduction Hepatitis C is a blood-borne virus (HCV) that can seriously damage the liver and is spread mainly through blood-to-blood contact with an infected person. Over 85% of individuals who have HCV in Scotland became infected following injecting drug use. Since people who inject drugs (PWID) are the main source of new infections, theoretical modelling has suggested that treatment of HCV infection in PWID may effectively reduce HCV prevalence and accomplish elimination. This protocol describes a clinical trial delivering HCV treatment within injecting equipment provision sites (IEPS) in Tayside, Scotland.Methods and analysis PWID attending IEPS are tested for HCV and, if they are chronically infected with HCV and eligible, invited to receive treatment within the IEPS. They are randomised to one of three treatment regimens; daily observed treatment, treatment dispensed every 2 weeks and treatment dispensed every 2 weeks together with an adherence psychological intervention (administered before treatment begins). The primary outcome is comparison of the rate of successful treatment (SVR12) in each treatment group. Secondary analyses include assessment of adherence, reinfection rates, viral resistance to treatment and interaction of the treatment with illicit drugs.Ethics and dissemination The ADVANCE (A Direct obserVed therApy versus fortNightly CollEction) HCV trial was given favourable opinion by East of Scotland Research Ethics Committee (LR/17/ES/0089) prior to commencement.Trial registration numbers European Clinical Trials Database (EudraCT) (2017-001039-38) and ClinicalTrials.gov (NCT03236506).

Background: Ankle sprains are very common injuries. Although recovery can occur within weeks, around one-third of patients have longer-term problems. Objectives: To develop and externally validate a prognostic model for identifying people at increased risk of poor outcome after an acute ankle sprain. Design: Development of a prognostic model in a clinical trial cohort data set and external validation in a prospective cohort study. Setting: Emergency departments (EDs) in the UK. Participants: Adults with an acute ankle sprain (within 7 days of injury). Sample size: There were 584 clinical trial participants in the development data set and 682 recruited for the external validation study. Predictors: Candidate predictor variables were chosen based on availability in the clinical data set, clinical consensus, face validity, a systematic review of the literature, data quality and plausibility of predictiveness of the outcomes. Main outcome measures: Models were developed to predict two composite outcomes representing poor outcome. Outcome 1 was the presence of at least one of the following symptoms at 9 months after injury: persistent pain, functional difficulty or lack of confidence. Outcome 2 included the same symptoms as outcome 1, with the addition of recurrence of injury. Rates of poor outcome in the external data set were lower than in the development data set, 7% versus 20% for outcome 1 and 16% versus 24% for outcome 2. Analysis: Multiple imputation was used to handle missing data. Logistic regression models, together with multivariable fractional polynomials, were used to select variables and identify transformations of continuous predictors that best predicted the outcome based on a nominal alpha of 0.157, chosen to minimise overfitting. Predictive accuracy was evaluated by assessing model discrimination (c-statistic) and calibration (flexible calibration plot). Results: (1) Performance of the prognostic models in development data set – the combined c-statistic for the outcome 1 model across the 50 imputed data sets was 0.74 [95% confidence interval (CI) 0.70 to 0.79], with good model calibration across the imputed data sets. The combined c-statistic for the outcome 2 model across the 50 imputed data sets was 0.70 (95% CI 0.65 to 0.74), with good model calibration across the imputed data sets. Updating these models, which used baseline data collected at the ED, with an additional variable at 4 weeks post injury (pain when bearing weight on the ankle) improved the discriminatory ability (c-statistic 0.77, 95% CI 0.73 to 0.82, for outcome 1 and 0.75, 95% CI 0.71 to 0.80, for outcome 2) and calibration of both models. (2) Performance of the models in the external data set – the combined c-statistic for the outcome 1 model across the 50 imputed data sets was 0.73 (95% CI 0.66 to 0.79), with a calibration plot intercept of –0.91 (95% CI –0.98 to 0.44) and slope of 1.13 (95% CI 0.76 to 1.50). The combined c-statistic for the outcome 2 model across the 50 imputed data sets was 0.63 (95% CI 0.58 to 0.69), with a calibration plot intercept of –0.25 (95% CI –0.27 to 0.11) and slope of 1.03 (95% CI 0.65 to 1.42). The updated models with the additional pain variable at 4 weeks had improved discriminatory ability over the baseline models but not better calibration. Conclusions: The SPRAINED (Synthesising a clinical Prognostic Rule for Ankle Injuries in the Emergency Department) prognostic models performed reasonably well, and showed benefit compared with not using any model; therefore, the models may assist clinical decision-making when managing and advising ankle sprain patients in the ED setting. The models use predictors that are simple to obtain. Limitations: The data used were from a randomised controlled trial and so were not originally intended to fulfil the aim of developing prognostic models. However, the data set was the best available, including data on the symptoms and clinical events of interest. Future work: Further model refinement, including recalibration or identifying additional predictors, may be required. The effect of implementing and using either model in clinical practice, in terms of acceptability and uptake by clinicians and on patient outcomes, should be investigated. Trial registration: Current Controlled Trials ISRCTN12726986. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 64. See the NIHR Journals Library website for further project information. Funding was also recieved from the NIHR Collaboration for Leadership in Applied Health Research, Care Oxford at Oxford Health NHS Foundation Trust, NIHR Biomedical Research Centre, Oxford, and the NIHR Fellowship programme.

Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for heart failure (HF). Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission) was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona) over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR) for the associations between NAFLD and the outcome(s) of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes). Patients with NAFLD (n = 109; 51.4%) had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, p

BACKGROUND:High sugar and refined carbohydrate intake is associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular mortality. Reducing the health impact of poor quality carbohydrate intake is a public health priority. Reducose, a proprietary mulberry leaf extract (ME), may reduce blood glucose responses following dietary carbohydrate intake by reducing absorption of glucose from the gut. METHODS:A double-blind, randomised, repeat measure, phase 2 crossover design was used to study the glycaemic and insulinaemic response to one reference product and three test products at the Functional Food Centre, Oxford Brooks University, UK. Participants; 37 adults aged 19-59 years with a BMI ≥ 20kg/m2 and ≤ 30kg/m2. The objective was to determine the effect of three doses of mulberry-extract (Reducose) versus placebo on blood glucose and insulin responses when co-administered with 50g maltodextrin in normoglycaemic healthy adults. We also report the gastrointestinal tolerability of the mulberry extract. RESULTS:Thirty-seven participants completed the study: The difference in the positive Incremental Area Under the Curve (pIAUC) (glucose (mmol / L x h)) for half, normal and double dose ME compared with placebo was -6.1% (-18.2%, 5.9%; p = 0.316), -14.0% (-26.0%, -2.0%; p = 0.022) and -22.0% (-33.9%, -10.0%; p

Many factors influence physical attractiveness, including degree of symmetry and relative length of legs. We asked a sample of 112 young adults to rate the attractiveness of computer-generated female bodies that varied in terms of symmetry and leg-to-body ratio. These effects were confirmed. However, we also varied whether the person in the image was shown sitting or standing. Half of the participants were tested standing and the other half sitting. The difference in the posture of the participants increased the perceived attractiveness of the images sharing the same posture, despite the fact that participants were unaware that their posture was relevant for the experiment. We conclude that our findings extend the role of embodied simulation in social cognition to perception of attractiveness from static images.