Achieving transformative progress on sustainability goals is dependent on synergistic actions across multiple policy domains. This identifies requirements for more coherent and integrated approaches to sustainable management of natural resource (SMNR) across land and sea, including air, water, soil, and geological resources. The challenge is further emphasised by severity and cross-cutting dimensions of nature loss and climate change crises. To help address this challenge, a general systems-based framework for SMNR was developed to facilitate co-ordinated knowledge exchange across the science–policy interface. Inspiration was provided by the Wellbeing of Future Generations Act in Wales, which obligates major policy innovation to sustain intergenerational wellbeing at a level beyond the current UN SDGs, including robust formulation of target outcomes and indicators. The SMNR framework, therefore, aimed to cross-reference primary outcomes for ecosystem resilience, natural resource management, and human wellbeing. Outcomes were linked through a circular reinforcing systems loop emphasising both ‘nature’s contributions to people’ relationships (including ecosystem services) and adaptive regenerative actions working with natural processes. Candidate indicators representing key concepts were also defined. The framework was applied in Wales through systems mapping to show relationships across policy domains. This highlighted added value of linked headline indicators with hierarchical components, exemplified by resource footprint metrics. Key issues from stakeholder engagement included long-term ‘reference conditions’, cross-scale integration, and inclusivity through multiple values. Major knowledge gaps exist regarding diverse relationships between nature and wellbeing, together with associated behaviours and actions, and hence efficacy of different actions for regenerating both natural and social systems. These issues highlight the need for flexibility, ongoing learning and adaptive capacity as integral to regenerative systems design.

INTRODUCTION:A novel referral pathway for exhibited breast symptom (EBS) referrals to manage increasing referrals of urgent suspected cancer (USC) was implemented in our trust. We report on the safety and effect on compliance with the 2-week-wait rule (2WW). METHODS:A single-centre longitudinal observational study included all patients referred to a UK breast unit during 13 May 2019 to 27 March 2020 (period 1) and 8 February 2021 to 31 January 2022 (period 2). USC referrals were assessed in a one-stop clinic (red flag clinic [RFC]); EBS referrals were assessed in a new clinic in which clinical evaluation was performed and imaging occurred subsequently (blue flag clinic [BFC]). Patients were followed up to determine the symptomatic interval cancer rate. RESULTS:There were 9,695 referrals; 1,655 referrals (17%) were assessed in the BFC after 63 exclusions. Some 95.9% of patients had a benign clinical examination (P1/P2), 80.1% had imaging (mammogram or ultrasound) and 4% had a tissue biopsy. In total, 16/1,655 (0.97%) BFC patients and 510/7,977 (8.2%) RFC patients were diagnosed with breast cancer (breast cancer detection rate). Some 1,631 patients (with 1,639 referrals) were discharged and followed up for a median of 17 months (interquartile range 12-32) with one subsequent cancer diagnosis (symptomatic interval cancer rate, 0.06%). Implementation of the BFC pathway increased 3-month average trust performance of USC referrals with 2WW standard from 8.5% to 98.7% (period 1) and from 30% to 66% (period 2). CONCLUSIONS:The BFC pathway for EBS patients is safe and implementation led to improvement against the 2WW target for USC referrals, ensuring resources are prioritised to patients with the highest likelihood of breast cancer.

To inform policy priorities, climate change risk assessments are often framed through an adaptation gap between current planned actions and those required to manage risk effectively. Residual risks remain to be managed through autonomous and reactive responses. Adaptation policies therefore assume a level of risk tolerance, but this is usually not made explicit. This lack of transparency can lead to a mismatch in expectations, especially when risk is increasing or perceived differently from experts. It also constrains wider engagement in adaptation decisions. These issues are explored both conceptually and through a UK case study referencing the third National Adaptation Programme whose generalised objectives demonstrate a policy delivery paradox that has also been subject to legal challenge. The paradox is exemplified by top-down objectives for resilience building or risk reduction that are ambiguous on assumed risk tolerance thresholds and implications for managing residual risks across all of society. A case is therefore made that both risk assessments and policy frameworks need explicit declarations on assumed risk tolerance and its implications, especially regarding those bearing the risks. This openness would be consistent with calls for an ‘honest conversation’ on expectations and viability of risk management outcomes between policy, stakeholders and public. Deliberation may involve difficult normative issues, especially to reconcile increasing risks against current resource constraint challenges. But it is ultimately necessary for wider societal adaptation engagement and increased adaptive capacity, including aspirations for enhanced collective resilience. Recommendations are hence provided to better explicate risk tolerance distinctions in adaptation research and policy.

Aims Vascular compromise due to arterial injury is a rare but serious complication of a proximal humeral fracture. The aims of this study were to report its incidence in a large urban population, and to identify clinical and radiological factors which are associated with this complication. We also evaluated the results of the use of our protocol for the management of these injuries. Methods A total of 3,497 adult patients with a proximal humeral fracture were managed between January 2015 and December 2022 in a single tertiary trauma centre. Their mean age was 66.7 years (18 to 103) and 2,510 (72%) were female. We compared the demographic data, clinical features, and configuration of those whose fracture was complicated by vascular compromise with those of the remaining patients. The incidence of vascular compromise was calculated from national population data, and predictive factors for its occurrence were investigated using univariate analysis. Results A total of 18 patients (0.5%) had a proximal humeral fracture and clinical evidence of vascular compromise, giving an annual incidence of 0.29 per 100,000 of the population. Their mean age was 68.7 years (45 to 92) and ten (56%) were female. Evidence of a mixed pattern neurological deficit (brachial plexus palsy) (odds ratio (OR) 380.6 (95% CI 85.9 to 1,685.8); p < 0.001), complete separation of the proximal shaft from the humeral head with medial displacement (OR 39.5 (95% CI 14.0 to 111.8); p < 0.001), and a fracture- dislocation (OR 5.0 (95% CI 1.6 to 15.3); p = 0.015) were all associated with an increased risk of associated vascular compromise. A policy of reduction and fixation of the fracture prior to vascular surgical intervention had favourable outcomes without vascular sequelae. Conclusion The classic signs of distal ischaemia are often absent in patients with proximal injuries to major vessels. We were able to identify specific clinical and radiological 'red flags' which, particularly when present in combination, should increase the suspicion of a fracture with an associated vascular injury, and facilitate early diagnosis and appropriate combined orthopaedic and vascular intervention.

Climate change-induced impacts on water quality challenge risk management of drinking water. Uncertainty around future changes and limited resources require approaches that enable prioritisation at regional or national scale for planning and adaptive intervention. This paper presents a framework for risk screening drinking water supplies, providing a staged approach to building the capacity for integrating climate change into risk management. The framework is applied to drinking water sources of the Scottish national drinking water provider, developing raw water trajectories for indicative water-quality parameters (water colour and Escherichia coli). It establishes baseline understanding of water-quality controls through multivariate statistical analysis. It incorporates climate and land-use change into the model using climate (UKCP18) and land-use projections. The results suggest potential higher organic carbon production in soils from increased production with higher temperature, combined with reduced dilution and drought effects from reductions in summer rainfall. For E. coli, risks arise through land-use change leading to potential agricultural intensification. The framework supports the targeted development of climate-resilient water safety plans, prioritising systems most at risk of raw water-quality deteriorations. It emphasises source protection to maintain or improve regulatory compliance, minimise socioeconomic and environmental harms, and generate additional benefits.

Introduction: Immediate implant-based reconstruction remains popular but is associated with high rates of implant loss and revision. It therefore requires careful patient selection and optimal technique. We have audited our single centre prepectoral reconstruction practice against national standards and iBra data.

3-3′-Diindolylmethane (DIM) is a biologically active dimer derived from the endogenous conversion of indole-3-carbinol (I3C), a naturally occurring glucosinolate found in many cruciferous vegetables (i.e., Brassicaceae). DIM was the first pure androgen receptor antagonist isolated from the Brassicaceae family and has been recently investigated for its potential pharmacological use in prostate cancer prevention and treatment. Interestingly, there is evidence that DIM can also interact with cannabinoid receptors. In this context, by considering the well-known involvement of the endocannabinoid system in prostate cancer, we have pharmacologically characterized the properties of DIM on both CB1 and CB2 cannabinoid receptors in two human prostate cancer cell lines: PC3 (androgen-independent/androgen receptor negative) and LNCaP (androgen-dependent). In the PC3 cell line, DIM was able to activate CB2 receptors and potentially associated apoptotic pathways. On the other hand, although DIM was also able to activate CB2 receptors in the LNCaP cell line, no apoptotic effects were observed. Our evidence confirms that DIM is a CB2 receptor ligand and, moreover, it has a potential anti-proliferative effect on androgen-independent/androgen receptor-negative prostate cancer cells.

Introduction: Axillary lymph node dissection (ALND) is associated with significant morbidity. Randomised data [1,2] suggest that axillary radiotherapy (RT), or no further axillary treatment beyond sentinel node biopsy (SNB) may be safe. There are very few studies to guide the management of preoperatively diagnosed lymph node metastases either in the context of neoadjuvant chemotherapy (NACT) or direct to surgery. The current UK recommendation is for ALND. In 2015 our policy changed to RT for carefully selected patients after MDT discussion. These data look at axillary recurrence for those patients having axillary RT Methods: Data were retrospectively collected on patients with preoperatively diagnosed lymph node metastases between January 2016 and December 2020. Patients undergoing surgery with a curative intent were included. The decision to offer axillary RT was made in the MDT based on clinical and radiological findings and the burden of disease in the axillary sample. Axillary recurrence was defined as disease recurring in the axilla with no distant disease. Results: Date were collected on 132 patients. Demographics and tumour status are outlined in Table 1. 55% of patients had neoadjuvant chemotherapy with a 52% path CR in the axilla. Table 2 gives the results for the axillary RT group. During the same time period 25 patient had ALND. Of those 2 (8%) had isolated LN recurrence. 18 patients had axillary RT following positive SLN after NACT. There was a single patient with axillary recurrence in this group. Conclusion: In the absence of randomised data to guide practice, these data show that in selected patients axillary radiotherapy is safe after axillary node sampling. The decision should be based on axillary burden, tumour biology, MDT and patient discussion. We await with interest the results of the Alliance A011202 trial to guide practice in patients having NACT in N1 disease. [1] Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. [2] Giuliano, A.E.; Ballman, K.; McCall, L.; Beitsch, P.; Whitworth, P.W.; Blumencranz, P.; Leitch, A.M.; Saha, S.; Morrow, M.; Hunt, K.K. Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Ann. Surg. 2016, 264, 413–420 Table 1. Demographics and tumour status. Table 2. Patients having Axillary RT. Citation Format: Hamza A. Arabiyat, Iain Brown, Philip Drew, Rachel English, Mona Sulieman, Imran Abbas, Duncan Wheatley, Kali Potiszil, Alastair Thomson, Polly King. Axillary radiotherapy in selected patients with a preoperative diagnosis of lymph node involvement is a safe alternative to axillary lymph node dissection [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-17.

Background: The incidence of breast ductal Carcinoma in Situ (DCIS) has been increasing; it currently represents up to 20-25% of all breast carcinomas. Encysted papillary cancer (EPC) is a rare form of breast carcinoma previously compared to DCIS which has been shown to present histologically with invasion of the basement membrane and even metastasis.Aims:Our objective was to define a ‘high risk’ group of patients with pre-op diagnosis of non-invasive cancer undergoing breast conserving surgery (BCS), who would then benefit from SLNB. Methods: A retrospective data collection including all the patients with DCIS over the last 5 years was performed. High risk was defined as: Extensive micro-calcification>40mm or any mass forming DCIS. EPC patients were collected via a Winpath search.

Introduction: Randomised data exists to support axillary radiotherapy (RT) or no further axillary treatment beyond sentinel node biopsy (SNB). Data are lacking to guide the management of cN1 disease. Current UK recommendation for pN1 disease post neoadjuvant chemotherapy (NACT) is ALND. In 2015 our policy changed to RT for selected patients after MDT discussion.

Introduction: Breast conserving therapy, has generally been accepted as treatment of choice for early invasive breast cancer. However adequate local control depends on obtaining negative margins and receipt of radiation In 20-30 % of patients with breast conserving surgery a second re-excision procedure is due to tumor-positive margins at histopathology. Margins re-excision rate are variable across the countries. Mean re-excision rate of 17.2% across units in UK. Intraoperative specimen radiography,used to evaluate partial mastectomy specimens ensure that the lesion is adequately removed. Objective: to determine whether 3D-intraoperative imaging better predicts margin status and reduces the re-excision rate than conventional 2D imaging. Methods: Retrospective study comparing two cohorts of patients 360 screen-detected breast cancer (2D cohort). April 2015 to March 2018 300 screen-detected breast cancer (3D cohort) April 2018 to March 2021 Royal Cornwall Hospital (RCHT) introduced a 3D intraoperative system for all cases in April 2018 Prior to the introduction of 3D intraoperative imaging at RCHT the re-excision rate was stable at approximately 15%. All patient had undergone preoperative digital mammogram and ultrasound. All patients had core biopsy diagnosis All malignancies were localised with ROLL (Radio-guided occult lesion localization) techniques. All wide local excision were performed by 5 fully trained oncoplastic breast surgeons (similar distribution within the two cohort) Specimen radiograph was performed intraoperatively using: 2D x-ray device (Faxitron system; Trident Hologic, Marlborough, MA) or 3D tomosynthesis (Mozart system; Kubtec Medical imaging, Stratford,CT). For both methods of assessment,specimen was placed in the device and auto exposed without any compression of tissue. All specimens were marked with orienting sutures and clips according to local protocol. All specimens were painted in theatre by the operating surgeon. All specimens were examined by the same pathologists. No change in margin protocol for 12 years(already compliant to ABS guidelines) • A clear margin for invasive cancer was defined as tumour found within 1mm of margin. For ductal carcinoma in situ (DCIS), a margin was classified as positive if ink on tumour, was classified as close ink is found in under 2 mm from tumour and as negative if more or equal to 2 mm, in accordance with NICE guidelines. (22) Statistical Analysis: • The study compares patient demographics, histology, and re-excision rates between 2D and 3D • Descriptive and comparative statistics are be calculated for all collected data TABLE 1: 3D/2D RR 0.59 (P:0.01), CI 0,3369-09068, Z -2.3473, P 0.0189 Conclusions: The use of intraoperative 3D specimen X-ray reduced the relative risk of re-excision rate by 41% (P=0.01) without any negative impact on other parameters. Table 1: Results 3D intraoperative imaging versus 2D intraoperative imaging Citation Format: Jo Mondani, Hamza Arabiyat, Stavroula Kastora, Mona Sulieman, Imran Abbas, Polly King, Rachel English, Iain Brown, Miklos Barta, Nicola Jackson, Philip Drew. 3-dimensional intraoperative analysis of screen-detected breast cancers reduce re-excision rates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-09.

• MBC, Accounts for 0.6% UK, 0.7 USA ,1% globally

To boost the application of machine learning (ML) techniques for credit scoring models, the blackbox problem should be addressed. The primary aim of this paper is to propose a measure based on counterfactuals to evaluate the interpretability of a ML credit scoring technique. Counterfactuals assist with understanding the model with regard to the classification decision boundaries and evaluate model robustness. The second contribution is the development of a data perturbation technique to generate a stress scenario. We apply these two proposals to a dataset on UK unsecured personal loans to compare logistic regression and stochastic gradient boosting (SBG). We show that training a blackbox model (SGB) as conditioned on our data perturbation technique can provide insight into model performance under stressed scenarios. The empirical results show that our interpretability measure is able to capture the classification decision boundary, unlike AUC and the classification accuracy widely used in the banking sector.

Habitat compensation schemes aim to offset unavoidable development-related losses at one site with replacement habitat elsewhere. They have become prominent policy tools used to address coastal squeeze of intertidal habitats occurring from sea-level rise and ‘hold-the-line’ management approaches. This policy development is evaluated against scientific evidence and its broader ethical dimensions regarding conservation of the natural environment. A case study is provided from the UK (England) where the National Habitat Compensation Programme aims to continue conservation obligations consistent with the EU Habitats Directive and Natura 2000. Progress is also referenced against Shoreline Management Plans and aspirations for a greater proportion of the coast to shift to managed realignment in response to sea level rise. Important barriers are identified, and issues of monitoring, transparency, and robustness are highlighted regarding habitat compensation and general coastal policy. At present, habitat compensation is based upon a simple area-based balance sheet approach which overlooks key uncertainties and gives a misleading indication of progress. Climate change adaptation planning needs to include more flexibility based upon alternative scenarios and response pathways, especially regarding recent evidence for higher future sea-level rises. Robust responses also require more emphasis on improved interpretation of ecological functioning, integrity, and coherence, as essential concepts to facilitate ecosystem-based adaptation consistent with international conventions and application of the precautionary principle.

National Climate Change Risk Assessments (CCRAs) have a key role in informing priorities for adaptation policy but face significant challenges due to multiple facets of risk and adaptation. Issues are especially pronounced for meeting goals of environmental sustainability due to the complex dynamics of socio-ecological systems. In practice, a CCRA can therefore differ from its original conceptual blueprint. These challenges are explored from a knowledge systems perspective, focusing on the role of stakeholders/policymakers, risk descriptors, methods, evidence sources, and scientists. A UK case study evaluates recent developments (CCRA3) including identification of policy urgency through adaptation shortfalls and its application to the natural environment. Important science-policy issues are also highlighted regarding inclusion of opportunities, systemic risks, residual risks, and risk tolerance. A general conclusion is that CCRAs inevitably leave open questions which lead back to their evolving role in the science-policy interface. A knowledge systems perspective identifies CCRAs as open, adaptive, reflexive processes that help redefine interpretations of risk and adaptation, rather than just providing a specific policy-relevant product. This perspective identifies scope for progressive refinement of CCRAs to enhance collective science-policy adaptive capacity whilst also engaging wider society. For environmental sustainability, this open process can be used to iteratively redefine robust future pathways and system reference conditions that also better reflect evolving societal perceptions and tolerance on sustainability risk in the face of climate change.

Background: Male breast cancer Audit , 10 years single centre experience