Now showing items 21-40 of 6409

    • Finite Element Modelling of a Cellular Electric Microenvironment.

      Verdes, Miruna; Disney, Catherine; Phamornnak, Chinnawich; Margetts, Lee; email:; Cartmell, Sarah; email: (2021-05-18)
      Clinical studies show electrical stimulation (ES) to be a potential therapy for the healing and regeneration of various tissues. Understanding the mechanisms of cell response when exposed to electrical fields can therefore guide the optimization of clinical applications. In vitro experiments aim to help uncover those, offering the advantage of wider input and output ranges that can be ethically and effectively assessed. However, the advancements in in vitro experiments are difficult to reproduce directly in clinical settings. Mainly, that is because the ES devices used in vitro differ significantly from the ones suitable for patient use, and the path from the electrodes to the targeted cells is different. Translating the in vitro results into in vivo procedures is therefore not straightforward. We emphasize that the cellular microenvironment's structure and physical properties play a determining role in the actual experimental testing conditions and suggest that measures of charge distribution can be used to bridge the gap between in vitro and in vivo. Considering this, we show how in silico finite element modelling (FEM) can be used to describe the cellular microenvironment and the changes generated by electric field (EF) exposure. We highlight how the EF couples with geometric structure to determine charge distribution. We then show the impact of time dependent inputs on charge movement. Finally, we demonstrate the relevance of our new in silico model methodology using two case studies: (i) in vitro fibrous Poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT-PSS) scaffolds and (ii) in vivo collagen in extracellular matrix (ECM).
    • Clinical trial protocol: PRednisolone in early diffuse cutaneous Systemic Sclerosis (PRedSS)

      Herrick, Ariane L; orcid: 0000-0003-4941-7926; email:; Griffiths-Jones, Deborah J; Ryder, W David; Mason, Justin C; Denton, Christopher P; orcid: 0000-0003-3975-8938 (SAGE Publications, 2020-09-17)
      Background:: Many of the painful, disabling features of early diffuse cutaneous systemic sclerosis have an inflammatory component and are potentially treatable with corticosteroid therapy. These features include painful and itchy skin, fatigue and musculoskeletal involvement. Yet many clinicians are understandably reluctant to prescribe corticosteroids because of the concern that these are a risk factor for scleroderma renal crisis. The aim of PRedSS (PRednisolone in early diffuse cutaneous Systemic Sclerosis) is to evaluate the efficacy and safety of moderate dose prednisolone in patients with early diffuse cutaneous systemic sclerosis, specifically whether moderate dose prednisolone is (a) effective in terms of reducing pain and disability, and improving skin score and (b) safe, with particular reference to renal function. Methods:: PRedSS is a Phase II, multicentre, double-blind randomised controlled trial which aims to recruit 72 patients with early diffuse cutaneous systemic sclerosis. Patients are randomised to receive either prednisolone (dosage approximately 0.3 mg/kg) or placebo therapy for 6 months. The two co-primary outcome measures are the difference in mean Health Assessment Questionnaire Disability Index at 3 months and the difference in modified Rodnan skin score at 3 months. Secondary outcome measures include patient reported outcome measures of itch, hand function, anxiety and depression, and helplessness. Results:: Recruitment commenced in December 2017 and after a slow start (due to delays in opening centres) 25 patients have now been recruited. Conclusion:: PRedSS should help to answer the question as to whether clinicians should or should not prescribe prednisolone in early diffuse cutaneous systemic sclerosis.
    • Vitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency – clinical and laboratory pitfalls

      Sobczyńska-Malefora, Agata; orcid: 0000-0001-7349-9517; Delvin, Edgard; McCaddon, Andrew; Ahmadi, Kourosh R.; Harrington, Dominic J.; orcid: 0000-0003-4786-9240 (Informa UK Limited, 2021-04-21)
    • Effect of combined home-based, overground robotic-assisted gait training and usual physiotherapy on clinical functional outcomes in people with chronic stroke: A randomized controlled trial

      Wright, Amy; orcid: 0000-0002-7006-6465; Stone, Keeron; Martinelli, Louis; Fryer, Simon; Smith, Grace; Lambrick, Danielle; Stoner, Lee; orcid: 0000-0002-0682-2270; Jobson, Simon; Faulkner, James; orcid: 0000-0002-3704-6737 (SAGE Publications, 2020-12-27)
      Objectives: To assess the effect of a home-based over-ground robotic-assisted gait training program using the AlterG Bionic Leg orthosis on clinical functional outcomes in people with chronic stroke. Design: Randomized controlled trial. Setting: Home. Participants: Thirty-four ambulatory chronic stroke patients who recieve usual physiotherapy. Intervention: Usual physiotherapy plus either (1)10-week over-ground robotic-assisted gait training program ( n = 16), using the device for ⩾30 minutes per day, or (2) control group ( n = 18), 30 minutes of physical activity per day. Measurements: The primary outcome was the Six-Minute Walk Test. Secondary outcomes included: Timed-Up-and-Go, Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale. Physical activity and sedentary time were assessed using accelerometry. All measurements were completed at baseline, 10 and 22 weeks after baseline. Results: Significant increases in walking distance were observed for the Six-Minute Walk Test between baseline and 10 weeks for over-ground robotic-assisted gait training (135 ± 81 m vs 158 ± 93 m, respectively; P ⩽ 0.001) but not for control (122 ± 92 m vs 119 ± 84 m, respectively). Findings were similar for Functional Ambulation Categories, Dynamic Gait Index and Berg Balance Scale (all P ⩽ 0.01). For over-ground robotic-assisted gait training, there were increases in time spent stepping, number of steps taken, number of sit-to-stand transitions, and reductions in time spent sitting/supine between baseline and 10 weeks (all P < 0.05). The differences observed in all of the aforementioned outcome measures were maintained at 22 weeks, 12 weeks after completing the intervention (all P > 0.05). Conclusion: Over-ground robotic-assisted gait training combined with physiotherapy in chronic stroke patients led to significant improvements in clinical functional outcomes and physical activity compared to the control group. Improvements were maintained at 22 weeks.
    • Nutrition knowledge and dietary intake of hurlers

      Murphy, John; orcid: 0000-0002-8337-722X; O’Reilly, James (SAGE Publications, 2020-11-26)
      The current study investigated the association between sports nutrition knowledge and dietary quality in a sample of adult Irish male hurling players. Nutrition knowledge was measured by the validated Sports Nutrition Knowledge Questionnaire (SNKQ). Diet quality was measured by the Australian Recommended Food Score (ARFS) calculated from food frequency questionnaire data. Analysis of variance and linear modelling were used to assess associations between variables. A total of 265 (129 elite, 136 sub-elite) players were recruited. No significant difference in nutrition knowledge (SNKQ) was found between groups. Results showed a significant difference (p = 0.02; d = 0.39 ± 0.25; small) in food score (ARFS) between groups. A weak, positive association (r = 0.3, p = 0.007) was found between nutrition knowledge and food score. Elite level players, aged 28–32, with college degrees, that have previously received nutritional guidance displayed the highest levels of both nutrition knowledge and food score. Higher levels of nutrition knowledge and food score were expected in elite players, however were only found in food score. Nutrition knowledge does contribute to dietary quality although future interventions should focus on specific gaps in knowledge such as how to meet total energy/carbohydrate requirements.
    • A Case Study of a Negotiated Tender within a Small-to-Medium Construction Contractor: Modelling Project Cost Variance

      Ellis, James; email:; Edwards, David John; email:; Thwala, Wellington Didibhuku; email:; Ejohwomu, Obuks; orcid: 0000-0001-7098-8999; email:; Ameyaw, Ernest Effah; email:; Shelbourn, Mark; email: (MDPI, 2021-06-18)
      This research explores the failure of competitively tendered projects in the UK construction industry to procure the most suited contractor(s) to conduct the works. Such work may have equal relevance for other developed nations globally. This research seeks to teach clients and their representatives that “lowest price” does not mean “best value”, by presenting a case study of a successfully negotiated tender undertaken by a small-to-medium enterprise (SME) contractor; SME studies are relatively scant in academic literature. By applying the “lessons learnt” principle, this study seeks to improve future practice through the development of a novel alternative procurement option (i.e., negotiation). A mixed philosophical stance combining interpretivism and pragmatism was used—interpretivism to critically review literature in order to form the basis of inductive research to discuss negotiation as a viable procurement route, and pragmatism to analyse perceptions of tendering and procurement. The methods used follow a three-stage waterfall process including: (1) literature review and pilot study; (2) quantitative analysis of case study data; and (3) qualitative data collection via a focus group. Our research underscores the need to advise clients and their representatives of the importance of understanding the scope of works allowed within a tender submission before discounting it based solely on price. In addition, we highlight the failings of competitive tendering, which results in increased costs and project duration once the works commence on site. These findings provide new contemporary insight into procurement and tendering in the construction industry, with emphasis on SME contractors, existing relationships, and open-book negotiation. This research illustrates the adverse effects of early cost estimates produced without first securing a true understanding of project buildability and programming. Our work concludes with a novel insight into an alternative procurement option that involves early SME contractor involvement in an open-book environment, without the need for a third-party cost control.
    • A Three-Year Longitudinal Study Comparing Bone Mass, Density, and Geometry Measured by DXA, pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes

      Daly, Anne; orcid: 0000-0003-2579-8699; email:; Högler, Wolfgang; orcid: 0000-0003-4328-6304; email:; Crabtree, Nicola; email:; Shaw, Nick; email:; Evans, Sharon; orcid: 0000-0002-7654-3621; email:; Pinto, Alex; email:; Jackson, Richard; email:; Ashmore, Catherine; email:; Rocha, Júlio C.; orcid: 0000-0002-4977-8345; email:; Strauss, Boyd J.; orcid: 0000-0002-5391-9681; email:; et al. (MDPI, 2021-06-17)
      In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2), bone mineral apparent density (L2–L4 BMAD g/cm3) and total body less head BMDa (TBLH g/cm2). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.
    • Lockdown, slow down: impact of the COVID-19 pandemic on physical activity-an observational study.

      Taylor, Joanne Kathryn; orcid: 0000-0001-9882-0119; email:; Ndiaye, Haarith; Daniels, Matthew; Ahmed, Fozia; Triage-HF Plus investigators (2021-06)
      In response to the COVID-19 pandemic, the UK was placed under strict lockdown measures on 23 March 2020. The aim of this study was to quantify the effects on physical activity (PA) levels using data from the prospective Triage-HF Plus Evaluation study. This study represents a cohort of adult patients with implanted cardiac devices capable of measuring activity by embedded accelerometery via a remote monitoring platform. Activity data were available for the 4 weeks pre-implementation and post implementation of 'stay at home' lockdown measures in the form of 'minutes active per day' (min/day). Data were analysed for 311 patients (77.2% men, mean age 68.8, frailty 55.9%. 92.2% established heart failure (HF) diagnosis, of these 51.2% New York Heart Association II), with comorbidities representative of a real-world cohort.Post-lockdown, a significant reduction in median PA equating to 20.8 active min/day was seen. The reduction was uniform with a slightly more pronounced drop in PA for women, but no statistically significant difference with respect to age, body mass index, frailty or device type. Activity dropped in the immediate 2-week period post-lockdown, but steadily returned thereafter. Median activity week 4 weeks post-lockdown remained significantly lower than 4 weeks pre-lockdown (p≤0.001). In a population of predominantly HF patients with cardiac devices, activity reduced by approximately 20 min active per day in the immediate aftermath of strict COVID-19 lockdown measures. NCT04177199. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.]
    • Flogging a Dead Salmon? Reduced Dose Posterior to Prostate Correlates With Increased PSA Progression in Voxel-Based Analysis of 3 Randomized Phase 3 Trials.

      Shortall, Jane; Palma, Giuseppe; Mistry, Hitesh; Vasquez Osorio, Eliana; McWilliam, Alan; Choudhury, Ananya; Aznar, Marianne; van Herk, Marcel; Green, Andrew; email: (2021-04-20)
    • The Impacts of the Early Outset of the COVID-19 Pandemic on Climate Change Research: implications for policy-making

      Filho, Walter Leal; orcid: 0000-0002-1241-5225; Wall, Tony; orcid: 0000-0003-2334-3279; Nagy, Gustavo J.; orcid: 0000-0002-8296-4465; Alves, Fatima; Carril, Luis Ricardo Fernández; orcid: 0000-0002-2078-4362; Li, Chunlan; Mucova, Serafino; Platje, Johannes; orcid: 0000-0002-6274-1467; Rayman-Bacchus, Lez; Totin, Edmond; et al.
      Since January 2020, the COVID-19 pandemic has dominated the media and exercises pressure on governments worldwide. Apart from its effects on economies, education systems and societies, the pandemic has also influenced climate change research. This paper examines the extent to which COVID-19 has influenced climate change research worldwide during the first wave at the beginning of 2020 and how it is perceived to exploit it in the future. This study utilised an international survey involving those dedicated to climate change science and management research from Academia, Government, NGOs, and international agencies in 83 countries. Results show that: (1) COVID-19 modified the way the surveyed researchers work, (2) there are indicators that COVID-19 has already influenced the direction of climate change and adaptation policy implementation, and (3) respondents perceived (explicitly concerning the COVID-19 lockdowns of March-April 2020), that the pandemic has drawn attention away from climate policy. COVID-19 has influenced the agenda of climate change research for more than half of the respondents and is likely to continue in the future, suggesting that the impacts on their research will still be felt for many years. The paper concludes by outlining critical implications for policy-making.
    • Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients.

      Wulandari, Laksmi; Hamidah, Berliana; Pakpahan, Cennikon; Damayanti, Nevy Shinta; Kurniati, Neneng Dewi; Adiatmaja, Christophorus Oetama; Wigianita, Monica Rizky; Soedarsono; Husada, Dominicus; Tinduh, Damayanti; et al. (2021-05-17)
      <h4>Background</h4>Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load.<h4>Results</h4>We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19.<h4>Conclusion</h4>Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.
    • Associate Teachers’ views on dialogic mentoring

      Jones, Luke; Tones, Steven; Foulkes, Gethin; Jones, Rhys C. (Informa UK Limited, 2021-06-02)
    • Sulfidation of magnetite with incorporated uranium.

      Townsend, Luke T; Morris, Katherine; Harrison, Robert; Schacherl, Bianca; Vitova, Tonya; Kovarik, Libor; Pearce, Carolyn I; Mosselmans, J Frederick W; Shaw, Samuel; email: (2021-02-26)
      Uranium (U) is a radionuclide of key environmental interest due its abundance by mass within radioactive waste and presence in contaminated land scenarios. Ubiquitously present iron (oxyhydr)oxide mineral phases, such as (nano)magnetite, have been identified as candidates for immobilisation of U via incorporation into the mineral structure. Studies of how biogeochemical processes, such as sulfidation from the presence of sulfate-reducing bacteria, may affect iron (oxyhydr)oxides and impact radionuclide mobility are important in order to underpin geological disposal of radioactive waste and manage radioactively contaminated land. Here, this study utilised a highly controlled abiotic method for sulfidation of U(V) incorporated into nanomagnetite to determine the fate and speciation of U. Upon sulfidation, transient release of U into solution occurred (∼8.6% total U) for up to 3 days, despite the highly reducing conditions. As the system evolved, lepidocrocite was observed to form over a period of days to weeks. After 10 months, XAS and geochemical data showed all U was partitioned to the solid phase, as both nanoparticulate uraninite (U(IV)O ) and a percentage of retained U(V). Further EXAFS analysis showed incorporation of the residual U(V) fraction into an iron (oxyhydr)oxide mineral phase, likely nanomagnetite or lepidocrocite. Overall, these results provide new insights into the stability of U(V) incorporated iron (oxyhydr)oxides during sulfidation, confirming the longer term retention of U in the solid phase under complex, environmentally relevant conditions. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • The city‐island‐state, wounding cascade, and multi‐level vulnerability explored through the lens of Malta

      Main, Geoff; orcid: 0000-0001-8453-1527; Schembri, John; Speake, Janet; Gauci, Ritienne; Chester, David (Wiley, 2021-05-06)
    • Heuristic assessment of psychological interventions in schools (HAPI Schools)

      Platt, Ian A.; orcid: 0000-0003-2497-6713; Kannangara, Chathurika; orcid: 0000-0001-6955-8158; Carson, Jerome; orcid: 0000-0002-7596-116X; Tytherleigh, Michelle; orcid: 0000-0003-2498-8175 (Wiley, 2021-05-02)
    • Management of ‘disorders of sex development’/intersex variations in children: Results from a freedom of information exercise

      Garland, Fae; orcid: 0000-0002-6725-7682; email:; Thomson, Michael; Travis, Mitchell; Warburton, Joshua (SAGE Publications, 2021-06-17)
      Non-therapeutic medical interventions on the bodies of children born with disorders of sex development (DSD)/intersex variations have been subject to increasing critical scrutiny. In response to recent criticism directed at the United Kingdom, and early moves to consider reform, we report on a freedom of information exercise that sought to evaluate whether National Health Service England is meeting international standards on optimal clinical management of DSD/intersex variations. The study explored what medical protocols are being followed to help inform potential reform, particularly with regard to non-therapeutic surgery. While the exercise revealed limited examples of promising practice, current protocols in the majority of Trusts appear unlikely to meet the complex needs of these children. We identify areas where significant improvement is needed, including data management, consistency in guideline use, composition of multidisciplinary teams and addressing disciplinary hierarchies within teams. These concerns sharpen criticisms of the lack of recognition of children’s rights in this context.
    • A Bayesian Estimation of Child Labour in India

      Kim, Jihye; email:; Olsen, Wendy; Wiśniowski, Arkadiusz (Springer Netherlands, 2020-06-18)
      Abstract: Child labour in India involves the largest number of children in any single country in the world. In 2011, 11.8 million children between the ages of 5 and 17 were main workers (those working more than 6 mo) according to the Indian Census. Our estimate of child labour using a combined-data approach is slightly higher than that: 13.2 million (11.4–15.2 million) for ages 5 to 17. There are various opinions on how best to measure the prevalence of child labour. In this study, we use the International Labour Organization (ILO)‘s methodology to define hazardousness and combine it with the most recent United Nations Children’s Fund (UNICEF)‘s time thresholds for economic work and household chores. The specific aims of this study are to estimate the prevalence of child labour in the age group 5 to 17 and to suggest a combined-data approach using Bayesian inference to improve the accuracy of the child labour estimation. This study combines the National Sample Survey on Employment and Unemployment 2011/12 and the India Human Development Survey 2011/12 and compares the result with the reported figures for the incidence of child labour from the Indian Census. Our unique combined-data approach provides a way to improve accuracy, smooth the variations between ages and provide reliable estimates of the scale of child labour in India.
    • The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

      Zhu, Bin; Poeta, Maria Luana; orcid: 0000-0002-6364-727X; Costantini, Manuela; Zhang, Tongwu; orcid: 0000-0003-2124-2706; Shi, Jianxin; Sentinelli, Steno; Zhao, Wei; orcid: 0000-0001-5103-3871; Pompeo, Vincenzo; Cardelli, Maurizio; orcid: 0000-0002-4480-2473; Alexandrov, Boian S.; orcid: 0000-0001-8636-4603; et al. (Nature Publishing Group UK, 2020-06-18)
      Abstract: Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance.
    • What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420)

      French, David P.; orcid: 0000-0002-7663-7804; email:; Astley, Susan; Brentnall, Adam R.; Cuzick, Jack; Dobrashian, Richard; Duffy, Stephen W.; Gorman, Louise S.; Harkness, Elaine F.; Harrison, Fiona; Harvie, Michelle; et al. (BioMed Central, 2020-06-18)
      Abstract: Background: In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict produces risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5 to < 8% 10-year) to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Despite the promise of systems such as BC-Predict, there are still too many uncertainties for a fully-powered definitive trial to be appropriate or ethical. The present research aims to identify these key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP. Key objectives of the present research are to quantify important potential benefits and harms, and identify key drivers of the relative cost-effectiveness of embedding BC-Predict into NHSBSP. Methods: A non-randomised fully counterbalanced study design will be used, to include approximately equal numbers of women offered NHSBSP (n = 18,700) and BC-Predict (n = 18,700) from selected screening sites (n = 7). In the initial 8-month time period, women eligible for NHSBSP will be offered BC-Predict in four screening sites. Three screening sites will offer women usual NHSBSP. In the following 8-months the study sites offering usual NHSBSP switch to BC-Predict and vice versa. Key potential benefits including uptake of risk consultations, chemoprevention and additional screening will be obtained for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires, with embedded qualitative process analysis. A decision-analytic model-based cost-effectiveness analysis will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHSBSP. Discussion: We will assess the feasibility of integrating BC-Predict into the NHSBSP, and identify the main uncertainties for a definitive evaluation of the clinical and cost-effectiveness of BC-Predict. Trial registration: Retrospectively registered with (NCT04359420).