Osteoarthritis is a leading cause of disability, most commonly affecting the articular cartilage of the knee in older individuals. Younger people are also at risk of developing post-traumatic osteoarthritis, including athletes and those with a history of joint injury. Focal cartilage defects can be treated through clinical interventions such as autologous chondrocyte implantation, where cells from the patient are isolated, cultured, and subsequently reimplanted into the defect site. Despite recent clinical advances, there is a lack of standardisation in the preparation of chondrocytes for cartilage tissue engineering therapies, with considerable variation in culture conditions reported in the literature. A major challenge in cell-based cartilage repair is the dedifferentiation of chondrocytes during monolayer expansion, which leads to a change in phenotype. Native articular chondrocytes exhibit a rounded morphology and express collagen type II and aggrecan, whilst dedifferentiated cells adopt a fibroblastic phenotype, characterised by an elongated morphology and increased expression of collagen type I. This review summarises the key physical, biochemical, and mechanical factors that mitigate chondrocyte dedifferentiation to support the maintenance of a chondrogenic phenotype and preserve the capacity of cells to redifferentiate. A mechanistically informed approach to chondrocyte culture will enhance cartilage tissue engineering therapies.

INTRODUCTION:Conflict-related sexual violence (CRSV) causes considerable physical and psychological harm, often leading to complex urogenital injuries that require specialised reconstructive surgery. Despite the growing global demand for specialised surgical care, access to niche specialities and training resources remain limited, particularly in high-conflict and resource-constrained areas. This study evaluates the effectiveness of the Accessible Novel Solutions for Widespread Emergency Reconstructive Surgery (ANSWERS) 3D-printed model, developed in collaboration with the Panzi Foundation, as a training tool for urogenital fistula repair associated with CRSV. METHODS:Conducted at Panzi Hospital in the Democratic Republic of Congo, this study employed a cross-sectional survey design involving 13 healthcare professionals. Participants engaged in hands-on practice with the 3D-printed model, creating and repairing simulated defects to closely replicate CRSV injuries. The survey assessed the model's anatomical fidelity, usability and impact on surgical preparedness, incorporating quantitative ratings and qualitative feedback. RESULTS:Our findings revealed strong support for the model's training value, with most participants reporting increased confidence in their technical skills. Areas for improvement due to limitations of anatomical detail and material durability were noted. Qualitative insights indicated that integrating the Panzi score-a classification system for fistula severity-and augmented reality or extended reality technology could enhance the model's relevance and interactivity. CONCLUSION:The study highlights the use of the ANSWERS 3D-printed model in building competency-based training protocols in CRSV care. Future refinements in the multilayered materials, novel bioengineering approaches to enhance biomimicry, anatomical accuracy based on CT scans and Panzi score classifications hold great potential. Ultimately, digital integrations could lead to the development of a standardised, immersive training curriculum that aligns with Panzi Hospital's holistic approach, improving surgical outcomes for CRSV survivors globally.

This observational cohort study explored lymphoedema development following a cancer diagnosis and whether demographic factors impacted the time to lymphoedema development. We identified cases through the Secure Anonymised Information Linkage (SAIL) Databank. We used cancer diagnostic codes to identify a cohort of six broad cancer 'types'. We independently used lymphoedema diagnostic codes to identify a cohort who developed lymphoedema. We linked these two cohorts to develop a single cohort of cases and describe the number of cases who went on to develop lymphoedema after a cancer diagnosis, and the time to lymphoedema diagnosis. We used Cox regression models to calculate hazard ratios and produced survival curves to explore whether pre-defined factors (gender, age, deprivation, cancer type) had any impact on time to lymphoedema development. We identified 7538 cases of lymphoedema development after a cancer diagnosis, relating to 7279 people. There was considerable variation in the time to diagnosis, with a mean and standard deviation of 483.3 (701.8) days. Cancer type was the single most important factor in explaining time to lymphoedema diagnosis. Time to lymphoedema was shortest in breast cancer. A large number of breast cancer cases have undergone surgery, and this may account for the earlier development of lymphoedema. Consideration should be made of risk factors for lymphoedema development in order to allow for more targeted treatment plans that could improve health-related quality of life for patients.

Nanocellulose (NC) possesses desirable biological and mechanical properties for 3D bioprinting. This study aimed to derive a novel NC-hyaluronic acid (HA) bioink for 3D bioprinting facial cartilages and assess its printability, biocompatibility and chondrogenicity. Pulp-derived NC blend was combined with a HA hydrogel to make composite NCHA bioinks ranging from 100 % HA to 20 % HA. Human nasoseptal chondrocytes were cultured in the bioinks for 21 days to assess chondrogenicity through gene expression analysis, quantitative protein assays and histology. Successful crosslinking using hydrogen peroxide solution (5 mu M) occurred within 5 min with no detriment to cell survival. All NCHA mixtures demonstrated increases in aggrecan, collagen and SOX9 expression over 21 days with bioinks comprising 20-40 % HA being the most chondrogenic (p = 0.0001). Printability was assessed using rheology and printability assays, demonstrating appropriate mechanical properties for 3D printing and shape retention as auricular cartilages. Biocompatibility with Live-Dead, lactate dehydrogenase and AlamarBlue assays demonstrated cell viability and proliferation sustained over 21 days. We conclude that NCHA bioinks promote chondrogenicity, possess favourable mechanical properties and have excellent biocompatibility for cartilage tissue engineering.

Nanocellulose has gained significant traction as a viable material for tissue engineering. We investigated 3 chemically distinct varieties of tunicate-derived nanocellulose: carboxymethylated (CTC), enzymatically pretreated (ETC), and TEMPO-oxidised (TTC), with the objective of determining a candidate scaffold material for tissue engineering. The physicochemical properties of each variant were characterised by SEM, AFM, Raman spectroscopy, and mechanical compression. Notably, ETC had the lowest aspect ratio, smallest pore diameter, greatest optical clarity, and highest ultimate compressive strength, indicating superiority as a candidate tissue engineering scaffold. Rheological analysis revealed a significantly higher loss tangent for ETC and reduced viscosity at higher temperature, compared with CTC and TTC. ETC also demonstrated superior line width resolution both before and after calcium chloride crosslinking, indicating superior print fidelity and post-printing shape retention. All materials exhibited excellent biological compatibility by live/dead staining of embedded primary chondrocytes. NC was nonimmunogenic and did not stimulate the secretion of proinflammatory mediators when combined with whole blood. The implantation of NC-based bioink into immunocompetent mice did not evoke an adverse immunological reaction, and explanted constructs retained a stable form for 14 days. Tunicate-derived NC, particularly ETC, demonstrates excellent structural, biological, and mechanical properties with great potential for tissue engineering applications.

IntroductionThe ability to bioprint facial cartilages could revolutionise reconstructive surgery, but identifying the optimum cell source remains one of the great challenges of tissue engineering. Tissue specific stem cells: chondroprogenitors, have been extracted previously using preferential adhesion to fibronectin based on the expression of CD49e: a perceived chondroprogenitor stem cell marker present on <1% of cartilage cells. This study sought to determine whether these fibronectin-adherent chondroprogenitor cells could be exploited for cartilage tissue engineering applications in isolation, or combined with differentiated chondrocytes.MethodsNasoseptal cartilage samples from 20 patients (10 male, 10 female) were digested to liberate cartilage-derived cells (CDCs) from extracellular matrix. Total cell number was counted using the Trypan Blue exclusion assay and added to fibronectin coated plates for 20 min, to determine the proportion of fibronectin-adherent (FAC) and non-adherent cells (NFACs). All populations underwent flow cytometry to detect mesenchymal stem/progenitor cell markers and were cultured in osteogenic, chondrogenic and adipogenic media to determine trilineage differentiation potential. Cell adherence and growth kinetics of the different populations were compared using iCELLigence growth assays. Chondrogenic gene expression was assessed using RT-qPCR for Type 2 collagen, aggrecan and SOX9 genes. Varying proportions of NFAC and FACs were cultured in alginate beads to assess tissue engineering potential.Results52.6% of cells were fibronectin adherent in males and 57.7% in females, yet on flow cytometrical analysis, only 0.19% of cells expressed CD49e. Moreover, all cells (CDC, FAC and NFACs) demonstrated an affinity for trilineage differentiation by first passage and the expression of stem/progenitor cell markers increased significantly from digest to first passage (CD29, 44, 49e, 73 and 90, p < 0.0001). No significant differences were seen in adhesion or growth rates. Collagen and aggrecan gene expression was higher in FACs than CDCs (2-fold higher, p = 0.008 and 0.012 respectively), but no differences in chondrogenic potential were seen in any cell mixtures in 3D culture models.ConclusionThe fibronectin adhesion assay does not appear to reliably isolate a chondroprogenitor cell population from nasoseptal cartilage, and these cells confer no advantageous properties for cartilage tissue engineering. Refinement of cell isolation methods and chondroprogenitor markers is warranted for future nasoseptal cartilage tissue engineering efforts.

Background The 2022 National Institute for Health and Care Excellence melanoma guideline update made significant changes to follow-up. The aim of this study was to assess the impact these changes will have on a national melanoma cohort over a 5-year follow-up interval.Methods Anonymized, individual-level, population-scale, linkable primary and secondary care National Health Service data for an 18-year interval (2000-2018) in Wales, UK were analysed. These data were used to predict the number of patients over a 10-year interval (2020-2030) that would be diagnosed with melanoma. Follow-up schedules for the 2015 and 2022 National Institute for Health and Care Excellence melanoma guidelines were then used to calculate the number of clinician-led appointments, the number of radiological investigations, and the total healthcare cost between 2025 and 2030, corresponding to a 5-year patient follow-up interval, for those with stage IA-IIC melanoma.Results Between 2025 and 2030 it is predicted that implementation of the 2022 guidelines would lead to 21 122 (range 19 194-23 083) fewer clinician-led appointments for patients with stage IA-IIC melanoma. However, there would be a significant increase in the number of radiological investigations (7812; range 7444-8189). These changes would lead to a euro2.74 million (euro1.87 million-euro3.61 million) reduction in the total cost of follow-up over the interval 2025-2030.Conclusion Melanoma follow-up guideline changes will result in a substantial reduction in the number of clinical follow-up appointments, but a significant additional burden to radiological services. The overall cost of follow-up at a national level will be reduced. Changes to the National Institute for Health and Care Excellence melanoma follow-up guidelines in 2022 will result in approximately 20 000 fewer clinician-led appointments over a 5-year interval in Wales. Despite the increase in radiology requirements, there will be a euro2.74 million reduction in healthcare cost.

The importance of written communication between clinicians and patients, especially in the wake of the Supreme Court case of Montgomery vs Lanarkshire, has led to a shift toward patient-centric care in the United Kingdom. This study investigates the use of large language models (LLMs) like ChatGPT and Google Bard in enhancing clinic letters with gold-standard complication profiles, aiming to improve patients' understanding and save clinicians' time in aesthetic plastic surgery. The aim of this study is to assess the effectiveness of LLMs in integrating complication profiles from authoritative sources into clinic letters, thus enhancing patient comprehension and clinician efficiency in aesthetic plastic surgery. Seven widely performed aesthetic procedures were chosen, and complication profiles were sourced from the British Association of Aesthetic Plastic Surgeons (BAAPS) and the American Society of Plastic Surgeons (ASPS). We evaluated the proficiency of the ChatGPT4, ChatGPT3.5, and Google Bard in generating clinic letters which incorporated complication profiles from online resources. These letters were assessed for readability using an online tool, targeting a recommended sixth-grade reading level. ChatGPT4 achieved the highest compliance in integrating complication profiles from BAAPS and ASPS websites, with average readability grades between eighth and ninth. ChatGPT3.5 and Google Bard showed lower compliance, particularly when accessing paywalled content like the ASPS Informed Consent Bundle. In conclusion, LLMs, particularly ChatGPT4, show promise in enhancing patient communications in aesthetic plastic surgery by effectively incorporating standard complication profiles into clinic letters. This aids in informed decision making and time saving for clinicians. However, the study underscores the need for improvements in data accessibility, search capabilities, and ethical considerations for optimal LLM integration into healthcare communications. Future enhancements should focus on better interpretation of inaccessible formats and a Human in the Loop approach to combine Artifical Intelligence capabilities with clinician expertise.Level of Evidence 3:

Introduction: Data supporting the current British Association of Dermatologists guidelines for the management of basal cell carcinoma (BCC) are based on historic studies and do not consider the updated Royal College of Pathologists (RCPath) histological reporting standards. The aim of this study was to use natural language processing (NLP)-derived data and undertake a multivariate analysis with updated RCPath standards, providing a contemporary update on the excision margins required to achieve histological clearance in BCC.Methods: A validated NLP information extraction model was used to perform a rapid multicentre, pan-specialty, consecutive retrospective analysis of BCCs, managed with surgical excision using a pre-determined clinical margin, over a 17-year period (2004-2021) at Swansea Bay University Health Board. Logistic regression assessed the relationship between the peripheralResults: We ran our NLP algorithm on 34,955 BCCs. Out of the 1447 BCCs that met the inclusion criteria, the peripheral margin clearance was not influenced by the BCC risk level (p = 0.670). A clinical peripheral margin of 6 mm achieved a 95% histological clearance rate (95% confidence interval [CI], 0.93-0.98). Tumour thickness inversely affected deep-margin histological clearance (OR 0.720, 95% CI, 0.525-0.991, p < 0.05). Depth level 2 had a 97% probability of achieving deep-margin histological clearance across all tumour thicknesses. Conclusion: Updated RCPath reporting standards minimally impact the peripheral margin histological clearance in BCC. Larger clinical peripheral margins than those indicated by current guidelines may be necessary to achieve excision rates of >= 95%. These findings emphasise the need for continuous reassessment of clinical standards to enhance patient care. (c) 2023 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.

Introduction: This study aimed to determine whether a dynamic orbital shaking culture system could enhance the cartilage production and viability of bioengineered nasoseptal cartilage.Methods: Human nasal chondrocytes were seeded onto nanocellulose-alginate biomaterials and cultured in static or dynamic conditions for 14 days. Quantitative polymerase chain reaction for chondrogenic gene expression (type 2 collagen, aggrecan and SOX9) was performed, demonstrating a transient rise in SOX9 expression at 1 and 7 days of culture, followed by a rise at 7 and 14 days in Aggrecan (184.5-fold increase, p < 0.0001) and Type 2 Collagen (226.3-fold increase, p = 0.049) expression. Samples were analysed histologically for glycosaminoglycan content using Alcian blue staining and demonstrated increased matrix formation in dynamic culture.Results: Superior cell viability was identified in the dynamic conditions through live-dead and alamarBlue assays. Computational analysis was used to determine the shear stress experienced by cells in the biomaterial in the dynamic conditions and found that the mechanical stimulation exerted was minimal (fluid shear stress <0.02 mPa, fluid pressure <48 Pa).Conclusion: We conclude that the use of an orbital shaking system exerts biologically relevant effects on bioengineered nasoseptal cartilage independently of the expected thresholds of mechanical stimulation, with implications for optimising future cartilage tissue engineering efforts.

Summary: There has been increased use of negative pressure wound therapy (NPWT) to aid closure of abdominoplasty incisions; this obviates previous complications, including delayed wound healing. We describe a reproducible method of NPWT-assisted wound healing applicable to abdominal wounds. We propose a modified method of NPWT application, specific to the to Avance Solo NPWT system, to achieve optimal wound healing by promoting a suitable environment and decreasing high-tension forces. Postoperatively, this technique enables patient and nursing ease owing to increased durability and drainless follow-up. This is further emphasized by the results of a quantitative analysis of a 100-patient case series measuring clinically relevant objective and patient-satisfaction outcomes, and the cost analysis of use.

Background Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case. Methods A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians. Results There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72). Conclusion This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as ‘human in the loop’ approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.

This article discusses the role of multidisciplinary teams in improving data flow to cancer registries and the inefficiencies of current retrospective data entry methods. It proposes a novel model using a rule-based natural language processing technique for basal cell carcinoma, integrating real-time analysis and structured data presentation to enhance national skin audit and data submission. The model faces challenges like varied reporting styles and the need for common ontologies but aims to fill a gap in dermatology and plastic surgery audits, improving healthcare quality through precise and timely data analysis.

Understanding the vascular anatomy of the face is crucial for ensuring safe clinical practices, especially as aesthetic procedures involving hyaluronic acid fillers are gaining popularity. Although vascular complications from these procedures are rare, there has been a documented increase in adverse events linked to venous and arterial occlusions. This review addresses the knowledge gap regarding the facial venous system compared to the well-documented facial artery system, emphasising the importance of thorough anatomical knowledge to mitigate risks during injectable cosmetic procedures. The complex and variable anatomy of the facial veins, including connections to the intracerebral venous system, allows for the retrograde spread of infections and fillers, with key tributaries such as the angular and infraorbital veins facilitating communication with the cavernous sinus. Notably, the absence of valves in certain venous regions can lead to retrograde filler flow, exacerbating complications. This illustrated review provides an analysis of the facial venous anatomy, focusing on the distribution and depth of venous structures, and aims to equip practitioners with insights that can help reduce the incidence of vascular complications associated with cosmetic procedures.

BACKGROUND:The Flapbot chatbot assists in free-flap monitoring, emphasizing accessibility, user-friendliness, and global reliability. This study assesses Flapbot's worldwide validity and usability and uses qualitative analysis to identify areas for future enhancement. METHODS:Flapbot, built on Google's DialogFlow, was evaluated by international plastic surgeons. Invitations were sent to the International Lower Limb Reconstruction Collaborative (INTELLECT), International Confederation of Plastic Surgery Societies (ICOPLAST), and the International Microsurgery Club. Out of the 42 surgeons who agreed to participate, 21 tested the Flapbot and completed an online survey on its validity and usability. The survey had 13 validity items and 10 usability items. Data analysis involved computing the individual content validity index (I-CVI) and scale-wide content validity index (S-CVI) for validity, and the system usability score (SUS) for usability. Thematic analysis distilled free-text responses to identify key themes. RESULTS:Nine of 13 items had an I-CVI over 0.78, denoting significant relevance. The S-CVI score stood at 0.82, indicating high relevance. The SUS score was 68, representing average usability. Themes highlighted issues with the current model, development suggestions, and surgeons' concerns regarding growing reliance on digital tools in health care. CONCLUSION:Flapbot is a promising digital aid for free-flap monitoring. While it showcases notable validity and usability, improvements in functionality, usability, and accessibility are needed for broader global use.

Background The psychological burden of cutaneous malignant melanoma (CM) is all-encompassing, affecting treatment adherence, recurrence and mortality. However, the prevalence and risk factors of anxiety and depression in CM remain unclear. Objectives To establish a benchmark pooled prevalence of anxiety and depression in CM, to provide magnitudes of association for clinical, therapeutic and demographic correlates, and to elucidate temporal trends in anxiety and depression from the time of diagnosis. Methods This review followed the MOOSE guidelines. MEDLINE, Embase, PsychINFO, Web of Science and the Cochrane Library were queried from database inception to 24 August 2023. Study selection, data extraction and quality assessment were performed by two independent authors, utilizing both the Joanna Briggs Institute (JBI) and National Institutes of Health risk-of-bias tools for the latter. The GRADE approach was used to rate the certainty of evidence. Prevalence rates, 95% confidence intervals (CIs) and prediction intervals (PIs) were derived using a random-effects model and estimating between- and within-study variance. Results Nine longitudinal and 29 cross-sectional studies were included (7995 patients). Based on the JBI and NIH tools, respectively, quality assessment found 20 and 17 to be at low risk of bias, 12 and 15 to be at moderate risk and 6 and 5 to be at high risk of bias. The prevalence of anxiety [30.6% (95% CI 24.6-37.0; PI 18-47%)] and depression [18.4% (95% CI 13.4-23.9; PI 10-33%)] peaked during treatment, declining to pretreatment levels after 1 year [anxiety: 48% vs. 20% (P = 0.005); depression: 28% vs. 13% (P = 0.03)]. Female sex [odds ratio (OR) 1.8, 95% CI 1.4-2.3; P < 0.001], age < 60 years (OR 1.5, 95% CI 1.2-2.0; P = 0.002) and low educational level (OR 1.5, 95% CI 1.2-2.0; P < 0.001) were likely to result in a large increase in the odds of anxiety. Depression was 12.3% higher in those with stage IV vs. those with stage I CM (P = 0.05). Relative to immune checkpoint inhibition, the rates of depression were 22% (P = 0.002) and 34% (P < 0.001) higher among patients with advanced-stage CM receiving interferon-alpha and chemotherapy, respectively. A significant reduction in self-reported depression scores was demonstrated over time (P = 0.003). Conclusions Notably, anxiety and depression in CM affect women, those younger than 60 years of age and the less educated, with up to 80% higher odds of anxiety in these groups. Anxiety and depression surge during chemotherapy and interferon treatment, especially in advanced CM. Our findings facilitate risk stratification and underscore the need for multidisciplinary vigilance.

IntroductionChildren with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder.MethodsA retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses.ResultsThere were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients.DiscussionMicrotia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced.

Can developments in natural language processing make data access easier andtransform how we use it?

BACKGROUND:There are 12.5 million people aged 65 years and older living in the UK. The annual incidence of open fracture is 30.7 per 10,000 person-years. In females, 42.9% of all open fractures occur in patients ≥ 65 years. METHODS AND MATERIALS:Preferred Reporting for Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study is registered with PROSPERO (CRD42020209149). The aim was to compare the complication profiles of free fasciocutaneous flaps and free muscular flaps in patients aged over 60 years undergoing lower limb soft tissue reconstruction following an open lower limb fracture. The search strategy based on strict inclusion criteria included PubMed, Embase and Google Scholar. RESULTS:15 papers were identified, including 46 patients with 10 free fasciocutaneous flaps and 41 free muscle flaps. There were 3 complications in the fasciocutaneous group (30%) and 9 complications in the muscle group (22%). There was a total of 1 secondary procedure in the fasciocutaneous group and 4 in the muscle group. DISCUSSION:There is insufficient data to provide statistical comparison between free fasciocutaneous versus free muscle flaps for lower limb reconstruction performed in those aged over 60 years. This systematic review highlights evidence for the successful use of free tissue transfer in the older population following an open fracture injury and requiring lower limb reconstruction. There is no evidence to suggest the superiority of one tissue type over the other, with the inference that well vascularised tissue is the most significant factor impacting outcome.