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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.

Single agent immune checkpoint inhibitors have been ineffective for patients with advanced stage and recurrent high grade serous ovarian cancer (HGSOC). Using pre-clinical models of HGSOC, we evaluated the anti-tumor and immune stimulatory effects of an oncolytic adenovirus, MEM-288. This conditionally replicative virus encodes a modified membrane stable CD40L and IFNβ. We demonstrated this virus successfully infects HGSOC cell lines and primary human ascites samples in vitro. We evaluated the anti-tumor and immunostimulatory activity in vivo in immune competent mouse models. Intraperitoneal delivery of MEM-288 decreased ascites and solid tumor burden compared to controls, and treatment generated a systemic anti-tumor immune response. The tumor microenvironment had a higher proportion of anti-tumor macrophages and decreased markers of angiogenesis. MEM-288 is a promising immunotherapy agent in HGSOC, with further pre-clinical studies required to understand the mechanism of action in the peritoneal microenvironment and clinical activity in combination with other therapies.

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

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.

Vascular complications from soft tissue fillers can have catastrophic consequences for patients. Adverse events are rare, but they are increasing, and their appearance may be the result of intravascular injection. A comprehensive understanding of the 2-dimensional anatomy (distribution) and 3-dimensional anatomy (depth) of the facial vasculature is fundamental for the safe delivery of nonsurgical cosmetic procedures. The purpose of this review is to provide an illustrated approach to examine surgical anatomy specific to the facial vascular system and the anatomical considerations clinicians need to give in specific danger during injectable cosmetic procedures. A grounding in safety and anatomy will help the new injector to mitigate the risk of vascular complications.

Abstract 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

Abstract Introduction At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. Methods and analysis A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. Primary outcome Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. Discussion This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Trial registration NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Introduction Amid clinicians’ challenges in staying updated with medical research, artificial intelligence (AI) tools like the large language model (LLM) ChatGPT could automate appraisal of research quality, saving time and reducing bias. This study compares the proficiency of ChatGPT3 against human evaluation in scoring abstracts to determine its potential as a tool for evidence synthesis.Methods We compared ChatGPT’s scoring of implant dentistry abstracts with human evaluators using the Consolidated Standards of Reporting Trials for Abstracts reporting standards checklist, yielding an overall compliance score (OCS). Bland-Altman analysis assessed agreement between human and AI-generated OCS percentages. Additional error analysis included mean difference of OCS subscores, Welch’s t-test and Pearson’s correlation coefficient.Results Bland-Altman analysis showed a mean difference of 4.92% (95% CI 0.62%, 0.37%) in OCS between human evaluation and ChatGPT. Error analysis displayed small mean differences in most domains, with the highest in ‘conclusion’ (0.764 (95% CI 0.186, 0.280)) and the lowest in ‘blinding’ (0.034 (95% CI 0.818, 0.895)). The strongest correlations between were in ‘harms’ (r=0.32, p

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.

Post-traumatic stress disorder (PTSD) is a trauma-related condition that produces distressing fear memory intrusions, avoidance behaviors, hyperarousal, stress responses, insomnia and other symptoms. This review of rodent models of PTSD examines trauma effects on fear-related learning, cognition, and avoidance, emotional and arousal behaviors and on mitochondrial dysfunction in relevant neural pathways. The review focuses on research that includes four elements: consensus PTSD rodent models, behavioral phenotyping, mitochondrial dysfunction within key neural regions. This approach allows for the integration of behavioral, neural and cellular findings in PTSD models. The PTSD models reviewed include fear conditioning, predator/social stress, chronic restraint stress, single prolonged stress, social isolation, chronic unpredictable stress and early life stress. These models produce a variety of PTSD-related behaviors that include associative and non-associative fear- and stress-related responses, hyperarousal, avoidance behaviors, cognitive disturbances, social withdrawal, compulsive behaviors, anhedonia-, anxiety- and depression-related behaviors. Neural regions included fear- and stress-related regions of the prefrontal cortex, hippocampal, amygdala, nucleus accumbens and hypothalamus. PTSD models produced mitochondrial dysfunction that includes dysregulation of oxidative phosphorylation and other metabolic pathways including β-oxidation of fatty acids and the tricarboxylic acid pathway. These models generated neural reactive oxygen species that damage DNA, proteins, and lipids. Trauma models further altered mitochondrial structure and replication and affected neuroinflammatory responses, signal transduction and apoptosis. Antidepressant medications used for the treatment of PTSD reversed stress-induced changes in some PTSD-like behaviors and many elements of brain mitochondrial dysfunction. Future studies can develop PTSD models which are ecologically valid and result in a broader manifestation of PTSD-related behaviors as it is clinically defined. This review highlights mitochondrial mechanisms associated with PTSD-like behaviors that have been produced in an array of consensus PTSD models and identifies putative circuit-based targets for more effective treatment for this debilitating disorder.

Three per cent hydrogen peroxide (H2O2) is widely used to irrigate acute and chronic wounds in the surgical setting and clinical experience tells us that it is more effective at removing dried-on blood than normal saline alone. We hypothesise that this is due to the effect of H2O2 on fibrin clot architecture via fibrinolysis. We investigate the mechanisms and discuss the clinical implications using an in vitro model. Coagulation assays with normal saline (NaCl), 1% and 3% concentrations of H2O2 were performed to determine the effect on fibrin clot formation. These effects were confirmed by spectrophotometry. The effects of 1%, 3% and 10% H2O2 on the macroscopic and microscopic features of fibrin clots were assessed at set time intervals and compared to a NaCl control. Quantitative analysis of fibrin networks was undertaken to determine the fibre length, diameter, branch point density and pore size. Fibrin clots immersed in 1%, 3% and 10% H2O2 demonstrated volume losses of 0.09-0.25mm3/min, whereas those immersed in the normal saline gained in volume by 0.02±0.13 mm3/min. Quantitative analysis showed that H2O2 affects the structure of the fibrin clot in a concentration-dependent manner, with the increase in fibre length, diameter and consequently pore sizes. Our results support our hypothesis that the efficacy of H2O2 in cleaning blood from wounds is enhanced by its effects on fibrin clot architecture in a concentration- and time-dependent manner. The observed changes in fibre size and branch point density suggest that H2O2 is acting on the quaternary structure of the fibrin clot, most likely via its effect on cross-linking of the fibrin monomers and may therefore be of benefit for the removal of other fibrin-dependent structures such as wound slough.

Abstract Weather forecasts made with imperfect models contain state‐dependent errors. Data assimilation (DA) partially corrects these errors with new information from observations. As such, the corrections, or “analysis increments,” produced by the DA process embed information about model errors. An attempt is made here to extract that information to improve numerical weather prediction. Neural networks (NNs) are trained to predict corrections to the systematic error in the National Oceanic and Atmospheric Administration's FV3‐GFS model based on a large set of analysis increments. A simple NN focusing on an atmospheric column significantly improves the estimated model error correction relative to a linear baseline. Leveraging large‐scale horizontal flow conditions using a convolutional NN, when compared to the simple column‐oriented NN, does not improve skill in correcting model error. The sensitivity of model error correction to forecast inputs is highly localized by vertical level and by meteorological variable, and the error characteristics vary across vertical levels. Once trained, the NNs are used to apply an online correction to the forecast during model integration. Improvements are evaluated both within a cycled DA system and across a collection of 10‐day forecasts. It is found that applying state‐dependent NN‐predicted corrections to the model forecast improves the overall quality of DA and improves the 10‐day forecast skill at all lead times.

IntroductionRoutinely collected healthcare data are a powerful research resource, but often lack detailed disease-specific information that is collected in clinical free text such as histopathology reports. We aim to use natural Language Processing (NLP) techniques to extract detailed clinical and pathological information from histopathology reports to enrich routinely collected data.MethodsWe used the general architecture for text engineering (GATE) framework to build an NLP information extraction system using rule-based techniques. During validation, we deployed our rule-based NLP pipeline on 200 previously unseen, de-identified and pseudonymised basal cell carcinoma (BCC) histopathological reports from Swansea Bay University Health Board, Wales, UK. The results of our algorithm were compared with gold standard human annotation by two independent and blinded expert clinicians involved in skin cancer care.ResultsWe identified 11,224 items of information with a mean precision, recall, and F1 score of 86.0% (95% CI: 75.1–96.9), 84.2% (95% CI: 72.8–96.1), and 84.5% (95% CI: 73.0–95.1), respectively. The difference between clinician annotator F1 scores was 7.9% in comparison with 15.5% between the NLP pipeline and the gold standard corpus. Cohen's Kappa score on annotated tokens was 0.85.ConclusionUsing an NLP rule-based approach for named entity recognition in BCC, we have been able to develop and validate a pipeline with a potential application in improving the quality of cancer registry data, supporting service planning, and enhancing the quality of routinely collected data for research.

IntroductionEarly exposure to practical skills in surgical training is essential in order to master technically demanding procedures such as the design and execution of local skin flaps. Changes in working patterns, increasing subspecializations, centralization of surgical services, and the publication of surgeon-specific outcomes have all made hands-on-training in a clinical environment increasingly difficult to achieve for the junior surgeon. This has been further compounded by the COVID-19 pandemic. This necessitates alternative methods of surgical skills training. To date, there are no standardized or ideal simulation models for local skin flap teaching.AimThis systematic review aims to summarize and evaluate local skin flap simulation and teaching models published in the literature.Materials and MethodsA systematic review protocol was developed and undertaken in accordance with PRISMA guidelines. Key search terms encompassed both “local skin flaps” and “models” or “surgical simulation”. These were combined using Boolean logic and used to search Embase, Medline, and the Cochrane Library. Studies were collected and screened according to the inclusion criteria. The final included articles were graded for their level of evidence and recommendation based on a modified educational Oxford Center for evidence-based medicine classification system and assessed according to the CRe-DEPTH tool for articles describing training interventions in healthcare professionals.ResultsA total of 549 articles were identified, resulting in the inclusion of 16 full-text papers. Four articles used 3D simulators for local flap teaching and training, while two articles described computer simulation as an alternative method for local flap practicing. Four models were silicone based, while gelatin, Allevyn dressings, foam rubber, and ethylene-vinyl acetate-based local flap simulators were also described. Animal models such as pigs head, porcine skin, chicken leg, and rat, as well as a training model based on fresh human skin excised from body-contouring procedures, were described. Each simulation and teaching method was assessed by a group of candidates via a questionnaire or evaluation survey grading system. Most of the studies were graded as level of evidence 3 or 4.ConclusionMany methods of simulation for the design and execution of local skin flaps have been described. However, most of these have been assessed only in small cohort numbers, and, therefore, larger candidate sizes and a standardized method for assessment are required. Moreover, some proposed simulators, although promising, are in a very preliminary stage of development. Further development and evaluation of promising high-fidelity models is required in order to improve training in such a complex area of surgery.

Abstract Background Since cartilage-derived stem/progenitor cells (CSPCs) were first identified in articular cartilage using differential adhesion to fibronectin, their self-renewal capacity and niche-specific lineage preference for chondrogenesis have propelled their application for cartilage tissue engineering. In many adult tissues, stem/progenitor cells are recognised to be involved in tissue homeostasis. However, the role of nasoseptal CSPCs has not yet been elucidated. Our aim was to isolate and characterise nasoseptal CSPCs alongside nasoseptal chondrocyte populations and determine chondrogenic capacity. Methods Here, we isolated nasoseptal CSPCs using differential adhesion to fibronectin and assessed their colony forming efficiency, proliferation kinetics, karyotype and trilineage potential. CSPCs were characterised alongside non-fibronectin-adherent nasoseptal chondrocytes (DNCs) and cartilage-derived cells (CDCs, a heterogenous combination of DNCs and CSPCs) by assessing differences in gene expression profiles using PCR Stem Cell Array, immunophenotype using flow cytometry and chondrogencity using RT-PCR and histology. Results CSPCs were clonogenic with increased gene expression of the neuroectodermal markers NCAM1 and N-Cadherin, as well as Cyclins D1 and D2, compared to DNCs. All three cell populations expressed recognised mesenchymal stem cell surface markers (CD29, CD44, CD73, CD90), yet only CSPCs and CDCs showed multilineage differentiation potential. CDC populations expressed significantly higher levels of type 2 collagen and bone morphogenetic protein 2 genes, with greater cartilage extracellular matrix secretion. When DNCs were cultured in isolation, there was reduced chondrogenicity and higher expression of type 1 collagen, stromal cell-derived factor 1 (SDF-1), CD73 and CD90, recognised markers of a fibroblast-like phenotype. Conclusions Fibronectin-adherent CSPCs demonstrate a unique gene expression profile compared to non-fibronectin-adherent DNCs. DNCs cultured in isolation, without CSPCs, express fibroblastic phenotype with reduced chondrogenicity. Mixed populations of stem/progenitor cells and chondrocytes were required for optimal chondrogenesis, suggesting that CSPCs may be required to retain phenotypic stability and chondrogenic potential of DNCs. Crosstalk between DNCs and CSPCs is proposed based on SDF-1 signalling.

Purpose: Bioprinting is becoming an increasingly popular platform technology for engineering a variety of tissue types. Our aim was to identify biomaterials that have been found to be suitable for extrusion 3D bioprinting, outline their biomechanical properties and biocompatibility towards their application for bioprinting specific tissue types. This systematic review provides an in-depth overview of current biomaterials suitable for extrusion to aid bioink selection for specific research purposes and facilitate design of novel tailored bioinks.Methods: A systematic search was performed on EMBASE, PubMed, Scopus and Web of Science databases according to the PRISMA guidelines. References of relevant articles, between December 2006 to January 2018, on candidate bioinks used in extrusion 3D bioprinting were reviewed by two independent investigators against standardised inclusion and exclusion criteria. Data was extracted on bioprinter brand and model, printing technique and specifications (speed and resolution), bioink material and class of mechanical assessment, cell type, viability, and target tissue. Also noted were authors, study design (in vitro/in vivo), study duration and year of publication.Results: A total of 9,720 studies were identified, 123 of which met inclusion criteria, consisting of a total of 58 reports using natural biomaterials, 26 using synthetic biomaterials and 39 using a combination of biomaterials as bioinks. Alginate (n = 50) and PCL (n = 33) were the most commonly used bioinks, followed by gelatin (n = 18) and methacrylated gelatin (GelMA) (n = 16). Pneumatic extrusion bioprinting techniques were the most common (n = 78), followed by piston (n = 28). The majority of studies focus on the target tissue, most commonly bone and cartilage, and investigate only one bioink rather than assessing a range to identify those with the most promising printability and biocompatibility characteristics. The Bioscaffolder (GeSiM, Germany), 3D Discovery (regenHU, Switzerland), and Bioplotter (EnvisionTEC, Germany) were the most commonly used commercial bioprinters (n = 35 in total), but groups most often opted to create their own in-house devices (n = 20). Many studies also failed to specify whether the mechanical data reflected pre-, during or post-printing, pre- or post-crosslinking and with or without cells.Conclusions: Despite the continued increase in the variety of biocompatible synthetic materials available, there has been a shift change towards using natural rather than synthetic bioinks for extrusion bioprinting, dominated by alginate either alone or in combination with other biomaterials. On qualitative analysis, no link was demonstrated between the type of bioink or extrusion technique and the target tissue, indicating that bioprinting research is in its infancy with no established tissue specific bioinks or bioprinting techniques. Further research is needed on side-by-side characterisation of bioinks with standardisation of the type and timing of biomechanical assessment.

Abstract Ensemble‐based data assimilation systems typically use covariance localization to dampen spurious correlations associated with sampling error while increasing the rank of the covariance estimate. Variational methods use model‐space localization, in which localization is applied to ensemble estimates of covariances between model variables and is based on distances between those variables, while ensemble filters apply observation‐space localization to estimates of model‐observation covariances, based on distances between model variables and observations. It has been shown that for nonlocal observations, such as satellite radiances, model‐space localization can be superior. This paper demonstrates a new method for performing model‐space localization in serial ensemble filters using the linearized observation operators (or Jacobians). Results of radiance‐only assimilation in a global forecast system show the benefit of using model‐space localization relative to observation‐space localization. The serial ensemble square root filter with vertical model‐space localization gives results similar to those of the Ensemble Variational system (without outer loops or extra balance constraints) while increasing the runtime compared to the filter with observation‐space localization by a factor between 2 and 8, depending on how sparse the Jacobian matrices are. The results are also similar to another approach to model‐space localization in ensemble filters: ensemble Kalman filter with modulated ensembles.

Importance: Reconstruction of facial deformity poses a significant surgical challenge due to the psychological, functional, and aesthetic importance of this anatomical area. There is a need to provide not only an excellent colour and contour match for skin defects, but also a durable cartilaginous structural replacement for nasal or auricular defects. The purpose of this review is to describe the history of, and state-of-the-art techniques within, facial cartilaginous surgery, whilst highlighting recent advances and future directions for this continually advancing specialty.Observations: Limitations of synthetic implants for nasal and auricular reconstruction, such as silicone and porous polyethylene, have meant that autologous cartilage tissue for such cases remains the current gold standard. Similarly, tissue engineering approaches using unrelated cells and synthetic scaffolds have shown limited in vivo success. There is increasing recognition that both the intrinsic and extrinsic microenvironment are important for tissue engineering and synthetic scaffolds fail to provide the necessary cues for cartilage matrix secretion.Conclusions and Relevance: We discuss the first-in-man studies in the context of biomimetic and developmental approaches to engineering durable cartilage for clinical translation. Implementation of engineered autologous tissue into clinical practise could eliminate donor site morbidity and represent the next phase of the facial reconstruction evolution.

Introduction: Previous studies of microtia epidemiology globally have demonstrated significant geographical and ethnic variation, cited broadly as affecting 3–5 in 10,000 live births. The aim of this study was to determine the incidence of microtia in a largely homogeneous ethnic population in the United Kingdom (Wales) and to identify factors, such as distance and socioeconomic status, which may influence the access to surgical intervention.Materials and Methods: A retrospective cohort study was conducted using data linkage to identify patients born between 2000 and 2018 with a diagnosis of microtia. Microtia 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. Sociodemographic attributes were compared using descriptive statistics to determine differences in access to each type of surgical intervention.Results: A total of 101 patients were identified, 64.4% were male and the median age was 12 (8–16). The mean annual incidence was 2.13 microtia cases per 10,000 births over the 19-year study period. Both temporal and geographic variation was noted. The majority of patients undergoing surgery opted for autologous reconstruction (72.9%) at a median age of 9 (7–10) compared to 7 (5–8) for prosthetic reconstruction. Autologous reconstruction had a higher median number of surgeries (2, 1–3) than prosthetic (1.5, 1–2) and a higher median socioeconomic status of 3 (2–4) compared to 2 (1–4) for the prosthetic cohort. There were no statistically significant differences in the distance traveled for surgery.Discussion: This study highlights a role for data linkage in epidemiological analyses and provides a revised incidence of microtia in Wales. Although the majority of patients opted for autologous reconstruction, demographic disparities in socioeconomic status warrant further investigation, emphasizing the importance of striving for equity in accessibility to surgical intervention.

Introduction: Plastic and reconstructive surgery is based on a culmination of technological advances, diverse techniques, creative adaptations and strategic planning. 3D imaging is a modality that encompasses several of these criteria while encouraging the others. Imaging techniques used in facial imaging come in many different modalities and sub-modalities which is imperative for such a complex area of the body; there is a clear clinical need for hyper-specialized practice. However, with this complexity comes variability and thus there will always be an element of bias in the choices made for imaging techniques.Aims and Objectives: The aim of this review is to systematically analyse the imaging techniques used in facial reconstruction and produce a comprehensive summary and comparison of imaging techniques currently available, including both traditional and novel methods.Methods: The systematic search was performed on EMBASE, PubMed, Scopus, Web of Science and Cochrane reviews using keywords such as “image technique/acquisition/processing,” “3-Dimensional,” “Facial,” and “Reconstruction.” The PRISMA guidelines were used to carry out the systematic review. Studies were then subsequently collected and collated; followed by a screening and exclusion process with a final full-text review for further clarification in regard to the selection criteria. A risk of bias assessment was also carried out on each study systematically using the respective tool in relation to the study in question.Results: From the initial 6,147 studies, 75 were deemed to fulfill all selection criteria and selected for meta-analysis. The majority of papers involved the use of computer tomography, though the use of magnetic resonance and handheld scanners using sonography have become more common in the field. The studies ranged in patient population, clinical indication. Seminal papers were highlighted within the group of papers for further analysis.Conclusions: There are clearly many factors that affect the choice of image acquisition techniques and their potential at being ideal for a given role. Ultimately the surgical team's choice will guide much of the decision, but it is crucial to be aware of not just the diagnostic ability of such modalities, but their treatment possibilities as well.

Introduction: The disciplines of 3D bioprinting and surgery have witnessed incremental transformations over the last century. 3D bioprinting is a convergence of biology and engineering technologies, mirroring the clinical need to produce viable biological tissue through advancements in printing, regenerative medicine and materials science. To outline the current and future challenges of 3D bioprinting technology in surgery.Methods: A comprehensive literature search was undertaken using the MEDLINE, EMBASE and Google Scholar databases between 2000 and 2019. A narrative synthesis of the resulting literature was produced to discuss 3D bioprinting, current and future challenges, the role in personalized medicine and transplantation surgery and the global 3D bioprinting market.Results: The next 20 years will see the advent of bioprinted implants for surgical use, however the path to clinical incorporation will be fraught with an array of ethical, regulatory and technical challenges of which each must be surmounted. Previous clinical cases where regulatory processes have been bypassed have led to poor outcomes and controversy. Speculated roles of 3D bioprinting in surgery include the production of de novo organs for transplantation and use of autologous cellular material for personalized medicine. The promise of these technologies has sparked an industrial revolution, leading to an exponential growth of the 3D bioprinting market worth billions of dollars.Conclusion: Effective translation requires the input of scientists, engineers, clinicians, and regulatory bodies: there is a need for a collaborative effort to translate this impactful technology into a real-world healthcare setting and potentially transform the future of surgery.

Abstract The ensemble Kalman filter (EnKF) has been widely used in atmosphere, ocean, and land applications. The observing network has been significantly developed, and thus, observations with highly dense temporal resolutions have become available. To better extract information from dense temporal observations, one straightforward strategy is to increase the assimilation frequency. However, more frequent assimilation may exacerbate the model imbalance and result in degraded forecasts. To combat the imbalance caused by ensemble‐based data assimilation due to sampling error and covariance localization, three‐ and four‐dimensional incremental analysis update (IAU) were proposed, which gradually introduce the analysis increments into model rather than intermittently updating the state. The trade‐off between the assimilation frequency and imbalance is systematically explored here by using an idealized two‐layer model and the NOAA GFS. Results from the idealized two‐layer model show that increasing assimilation frequency can reduce errors for state variables that are not sensitive to imbalances. For state variable that carries the signal of the external gravity mode and is sensitive to imbalances, increasing assimilation frequency without (with) IAU reduces (increases) errors. Without IAU, more frequent updates result in smaller increments and less insertion noise, while the initialization of IAU cannot effectively mitigate the imbalances with increased assimilation frequency. Results with a low‐resolution version of the NOAA GFS demonstrate that increasing assimilation frequency from 6 to 2 h improves the errors and biases of forecasts verified with conventional and radiance observations, although gravity wave noise in the forecast is increased.

Abstract Localization is essential to effectively assimilate satellite radiances in ensemble Kalman filters. However, the vertical location and separation from a model grid point variable for a radiance observation are not well defined, which results in complexities when localizing the impact of radiance observations. An adaptive method is proposed to estimate an effective vertical localization independently for each assimilated channel of every satellite platform. It uses sample correlations between ensemble priors of observations and state variables from a cycling data assimilation to estimate the localization function that minimizes the sampling error. The estimated localization functions are approximated by three localization parameters: the localization width, maximum value, and vertical location of the radiance observations. Adaptively estimated localization parameters are used in assimilation experiments with the National Centers for Environmental Prediction (NCEP) Global Forecast System (GFS) model and the National Oceanic and Atmospheric Administration (NOAA) operational ensemble Kalman filter (EnKF). Results show that using the adaptive localization width and vertical location for radiance observations is more beneficial than also including the maximum localization value. The experiment using the adaptively estimated localization width and vertical location performs better than the default Gaspari and Cohn (GC) experiment, and produces similar errors to the optimal GC experiment. The adaptive localization parameters can be computed during the assimilation procedure, so the computational cost needed to tune the optimal GC localization width is saved.

Objective: The aim of this study was to determine the validity of using a carvable 3D printed rib model in combination with a 3D printed auricular framework to facilitate the teaching, training and planning of auricular reconstruction.Design: 3D printed costal cartilages from ribs 6–9 were produced using a FormLabs Form3 Printer and used to make negative molds. 2:1 silicone-cornstarch mixture was added to each mold to make 12 simulated 6–9th costal cartilages suitable for carving. 3D printed auricular frameworks were produced in polylactic acid using an Ultimaker 3 3D printer to demonstrate the component parts and constructed framework of an auricular reconstruction.Participants: Twelve plastic surgery trainees attended a workshop in which they each attempted auricular reconstruction using the carvable models and 3D printed plastic models as a guide. All candidates completed a pre- and post-training questionnaire to assess confidence and comprehension of auricular reconstruction, and the suitability of the models for facilitating this teaching.Results: Only 42% of trainees (n = 5) had observed an ear reconstruction in theater prior to the training course. Statistically significant improvements in the appreciation of the different components that make an auricular framework (p < 0.0001) and confidence in carving and handling costal cartilage (p < 0.0001) were noted following completion of the training. Highly significant improvements in comprehension of the approach to ear reconstruction (p = 0.006) and locating the subunits of a reconstructed ear from costal cartilage (p = 0.003) were also noted. 100% of participants felt the 3D printed teaching aids directly enhanced their learning.Conclusions: Ear reconstruction is a complex, time consuming multi-stage operation demanding significant amounts of experience, planning and an appreciation of the 3D chondrocutaneous structure. In this study we have demonstrated the value of 3D printing in producing a suitable simulated costal cartilage model and as an adjunct to comprehending and planning a framework for auricular reconstruction.

Abstract Within the National Oceanic and Atmospheric Administration National Weather Service, the hybrid ensemble‐variational system (Gridpoint Statistical Interpolation, GSI) is run together with the 80‐member ensemble square root filter (EnSRF) operationally for the global forecast data assimilation system. EnSRF uses observation operator from GSI: current operational configuration requires 81 runs of GSI in the observation operator mode to run EnSRF (for each of the 80 ensemble members and for the ensemble mean). To reduce data assimilation cycle computation time, a GSI‐EnSRF configuration that requires a single run of the GSI system in the observation operator mode was developed. In this configuration EnSRF uses full observation operator for the ensemble mean and linearized observation operator for the ensemble perturbations. Comparison of the two approaches shows that using linearized observation operator for ensemble perturbations compared to using full observation operator does not change the analysis results significantly and allows to reduce overall data assimilation cycle computation time.

The pursuit of appropriate, biocompatible materials is one of the primary challenges in translational bioprinting. The requirement to refine a biomaterial into a bioink places additional demands on the criteria for candidate biomaterials. The material must enable extrusion as a liquid bioink and yet be capable of maintaining its shape in the post-printing phase to yield viable tissues, organs and biological materials. Plant-derived biomaterials show great promise in harnessing both the natural strength of plant microarchitecture combined with their natural biological roles as supporters of cell growth. The aim of this review article is to outline the most widely used biomaterials derived from land plants and marine algae: nanocellulose, pectin, starch, alginate, agarose, fucoidan, and carrageenan, with an in-depth focus on nanocellulose and alginate. The properties that render these materials as promising bioinks for three dimensional bioprinting is herein discussed alongside their potential in 3D bioprinting for tissue engineering, drug delivery, wound healing, and implantable medical devices.

The climate research community uses atmospheric reanalysis data sets to understand a wide range of processes and variability in the atmosphere, yet different reanalyses may give very different results for the same diagnostics. The Stratosphere–troposphere Processes And their Role in Climate (SPARC) Reanalysis Intercomparison Project (S-RIP) is a coordinated activity to compare reanalysis data sets using a variety of key diagnostics. The objectives of this project are to identify differences among reanalyses and understand their underlying causes, to provide guidance on appropriate usage of various reanalysis products in scientific studies, particularly those of relevance to SPARC, and to contribute to future improvements in the reanalysis products by establishing collaborative links between reanalysis centres and data users. The project focuses predominantly on differences among reanalyses, although studies that include operational analyses and studies comparing reanalyses with observations are also included when appropriate. The emphasis is on diagnostics of the upper troposphere, stratosphere, and lower mesosphere. This paper summarizes the motivation and goals of the S-RIP activity and extensively reviews key technical aspects of the reanalysis data sets that are the focus of this activity. The special issue The SPARC Reanalysis Intercomparison Project (S-RIP) in this journal serves to collect research with relevance to the S-RIP in preparation for the publication of the planned two (interim and full) S-RIP reports.

Thromboangiitis obliterans (TAO) is a vasculitis characterised by segmental occlusions of small to medium-sized arteries and superficial veins, and a curious predilection for young male smokers. The exact aetiology remains unknown. Current theories postulate it is an autoimmune endarteritis, triggered by some constituent of tobacco and occurring in genetically susceptible individuals. The disease can pose a diagnostic challenge, requiring a high degree of clinical suspicion, particularly in male smokers aged between 20-45 presenting with peripheral ischaemia. The fundamental principle of management is absolute tobacco abstinence. In this article, we report the case of a 27-year-old man who presented with infected, chronic wounds of his upper and lower extremities. He was initially treated with antibiotics and surgical debridement. Unfortunately he went on to develop a protracted course of complications due to poor wound healing ultimately leading to amputation of several digits. A diagnosis of TAO was suspected, and this was later confirmed histologically. Incidentally and of note, the patient was also found to be homo zygous for factor V Leiden. An association between TAO and hypercoagulable states, specifically hetero zygous factor V Leiden mutation, has been previously described. It is unclear if a synergistic effect between TAO and homozygosity for factor V Leiden may have contributed to the severity and unremitting nature of our patient’s symptoms. We present this case in order to highlight the importance of early recognition of the condition and the need to offer comprehensive smoking cessation support in order to prevent amputation and other complications of poor wound healing.

Background:. The keystone perforator island flap provides a versatile form of reconstruction. Perceived benefits include better donor-recipient color match, less contour defect, and fewer complications. To date, there has been no high-quality evidence comparing keystone flaps to split-thickness skin grafts (SSG) from both a qualitative and quantitative point of view. Methods:. The Objective and Patient Reported Assessments of Skin grafts versus Keystone flap cohort study compares keystone flaps with SSGs for the reconstruction of skin cancer defects. Patient-reported outcome measures were collected using the EuroQol 5 dimension scale and Patient and Observer Scar Assessment Scale (POSAS) questionnaires. Objective assessments of skin quality were assessed with the Courage and Khazaka system. Cost analysis was also performed. Results:. Thirty-eight patients were studied: 20 keystone flaps and 18 SSGs. The keystone group had higher EuroQol 5 dimension scale scores (keystone median = 1.0; SSG median = 0.832; P = 0.641) indicating better general quality of life and lower POSAS scores indicating better disease/condition specific quality of life (keystone mean = 27.7; SSG mean = 35.7; P = 0.323). Observer POSAS scores were significantly lower in the keystone group compared with the SSG group (keystone mean = 10.889; SSG mean = 17.313; P < 0.001). Preservation of sensation was significantly better in keystone flaps (P = 0.006). There was an average £158/$207 (15%) saving when performing a keystone flap. Conclusion:. This pilot study demonstrates a number of possible benefits of keystone flaps over SSGs. The results demonstrate the need for further research comparing these reconstructive options. We propose a prospective, controlled study using the methods developed in this pilot study.

ABSTRACT Fluoroquinolones (FQs) and ciprofloxacin (Cp) are important antimicrobials that pollute the environment in trace amounts. Although Cp has been recommended as prophylaxis for patients undergoing leech therapy to prevent infections by the leech gut symbiont Aeromonas, a puzzling rise in Cp-resistant (Cpr) Aeromonas infections has been reported. We report on the effects of subtherapeutic FQ concentrations on bacteria in an environmental reservoir, the medicinal leech, and describe the presence of multiple antibiotic resistance mutations and a gain-of-function resistance gene. We link the rise of Cpr Aeromonas isolates to exposure of the leech microbiota to very low levels of Cp (0.01 to 0.04 µg/ml),