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Understanding wind turbine wake recovery is important for developing models of wind turbine interaction employed in the design of energy-efficient wind farm layouts. Wake recovery is often assumed or explained to be a shear-driven process; however, this is generally not accurate. In this work we show that wind turbine wakes recover mainly due to the divergence (lateral and vertical gradients) of Reynolds shear stresses, which transport momentum from the freestream towards the wake center. The wake recovery mechanisms are illustrated using a simple analytic model and results of large-eddy simulation.

Reynolds-averaged Navier–Stokes (RANS) simulations of wind turbine wakes are usually conducted with two-equation turbulence models based on the Boussinesq hypothesis; these are simple and robust but lack the capability of predicting various turbulence phenomena. Using the explicit algebraic Reynolds stress model (EARSM) of Wallin and Johansson (2000) can alleviate some of these deficiencies while still being numerically robust and only slightly more computationally expensive than the traditional two-equation models. The model implementation is verified with the homogeneous shear flow, half-channel flow, and square duct flow cases, and subsequently full three-dimensional wake simulations are run and analyzed. The results are compared with reference large-eddy simulation (LES) data, which show that the EARSM especially improves the prediction of turbulence anisotropy and turbulence intensity but that it also predicts less Gaussian wake profile shapes.

In the past several years, wind veer – sometimes called “directional shear” – has begun to attract attention due to its effects on wind turbines and their production, particularly as the length of manufactured turbine blades has increased. Meanwhile, applicable meteorological theory has not progressed significantly beyond idealized cases for decades, though veer's effect on the wind speed profile has been recently revisited. On the other hand the shear exponent (α) is commonly used in wind energy for vertical extrapolation of mean wind speeds, as well as being a key parameter for wind turbine load calculations and design standards. In this work we connect the oft-used shear exponent with veer, both theoretically and for practical use. We derive relations for wind veer from the equations of motion, finding the veer to be composed of separate contributions from shear and vertical gradients of crosswind stress. Following from the theoretical derivations, which are neither limited to the surface layer nor constrained by assumptions about mixing length or turbulent diffusivities, we establish simplified relations between the wind veer and shear exponent for practical use in wind energy. We also elucidate the source of commonly observed stress–shear misalignment and its contribution to veer, noting that our new forms allow for such misalignment. The connection between shear and veer is further explored through analysis of one-dimensional (single-column) Reynolds-averaged Navier–Stokes solutions, where we confirm our theoretical derivations as well as the dependence of mean shear and veer on surface roughness and atmospheric boundary layer depth in terms of respective Rossby numbers. Finally we investigate the observed behavior of shear and veer across different sites and flow regimes (including forested, offshore, and hilly terrain cases) over heights corresponding to multi-megawatt wind turbine rotors, also considering the effects of atmospheric stability. From this we find empirical forms for the probability distribution of veer during high-veer (stable) conditions and for the variability in veer conditioned on wind speed. Analyzing observed joint probability distributions of α and veer, we compare the two simplified forms we derived earlier and adapt them to ultimately arrive at more universally applicable equations to predict the mean veer in terms of observed (i.e., conditioned on) shear exponent; lastly, the limitations, applicability, and behavior of these forms are discussed along with their use and further developments for both meteorology and wind energy.

Several recent studies have examined the steady-state welfare implications of mortality differentials within unfunded Social Security systems, concluding that these differentials undermine the progressivity of the system and make society worse-off relative to alternative public pension schemes. This study is the first to systematically investigate the long-run implications of mortality inequality within the U.S. Social Security system. Utilizing an OLG endogenous growth model of the U.S. economy, I compare the current pay-as-you-go (PAYG) system to versions of the model without either mortality differentials or income inequality. I find that the assumption of mortality homogeneity biases the equilibrium growth rate and welfare analysis. The PAYG system is also compared to a fully funded system based on capital subsidies. The model predicts that PAYG suppresses growth and that, for a given range of subsidy rates, the fully funded system Pareto dominates PAYG in both the medium-run and the long-run.

Circulating lactate is a fuel source for liver metabolism but may exacerbate metabolic diseases such as nonalcoholic steatohepatitis (NASH). Indeed, haploinsufficiency of lactate transporter monocarboxylate transporter 1 (MCT1) in mice reportedly promotes resistance to hepatic steatosis and inflammation. Here, we used adeno-associated virus (AAV) vectors to deliver thyroxin binding globulin (TBG)-Cre or lecithin-retinol acyltransferase (Lrat)-Cre to MCT1fl/flmice on a choline deficient, high fat NASH diet to deplete hepatocyte or stellate cell MCT1, respectively. Stellate cell MCT1KO (AAV-Lrat-Cre) attenuated liver type 1 collagen protein expression and caused a downward trend in trichrome staining. MCT1 depletion in cultured human LX2 stellate cells also diminished collagen 1 protein expression. Tetra-ethylenglycol-cholesterol (Chol)-conjugated siRNAs, which enter all hepatic cell types, and hepatocyte-selective tri-N-acetyl galactosamine (GN)-conjugated siRNAs were then used to evaluate MCT1 function in a genetically obese NASH mouse model. MCT1 silencing by Chol-siRNA decreased liver collagen 1 levels, while hepatocyte-selective MCT1 depletion by AAV-TBG-Cre or by GN-siRNA unexpectedly increased collagen 1 and total fibrosis without effect on triglyceride accumulation. These findings demonstrate that stellate cell lactate transporter MCT1 significantly contributes to liver fibrosis through increased collagen 1 protein expressionin vitroandin vivo, while hepatocyte MCT1 appears not to be an attractive therapeutic target for NASH.

The aim of this research is to investigate the pyrolytic reactivity of hemicellulose, specifically focusing on β-D-xylopyranose (xylose), as it is a significant component of hemicellulose. Quantum chemistry-based computational techniques, such as density functional theory, post Hartree-Fock methods, and composite schemes, were employed to evaluate the potential energy surfaces for the initial steps of xylose thermal degradation pathways. Conformational analysis of minima and transition states was carried out in order to obtain molecular structure guesses for global minima. To compare the accuracy of this study against other approaches, reference data was obtained from “cheap” composite schemes. In addition, the Arrhenius parameters were derived by fitting rate coefficients computed using transition state theory. These findings are beneficial and will be utilized in developing a kinetic model scheme in the near future.

BackgroundThere is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer.MethodsA prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery.ResultsComparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1–3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m2; Control 16.3 vs 14.7 kg/m2, p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed.ConclusionThe results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic.Trial registration numberNCT03626610.

Offshore wind farms are more commonly installed in wind farm clusters, where wind farm interaction can lead to energy losses; hence, there is a need for numerical models that can properly simulate wind farm interaction. This work proposes a Reynolds-averaged Navier-Stokes (RANS) method to efficiently simulate the effect of neighboring wind farms on wind farm power and annual energy production. First, a novel steady-state atmospheric inflow is proposed. This inflow model is well suited for RANS simulations of large wind farms because it does not lead to the development of nonphysical wind farm wakes. Second, a RANS-based wind farm parametrization is introduced, the actuator wind farm (AWF) model, which represents the wind farm as a forest canopy and allows to use of coarser grids compared to modeling all wind turbines as actuator disks (ADs). When the horizontal resolution of the RANS-AWF model is increased, the model results approach the results of the RANS-AD model. A double wind farm case is simulated with RANS to show that replacing an upstream wind farm with an AWF model only causes a deviation less than 1 % in terms of wind farm power of the downstream wind farm. Most importantly, a reduction in CPU hours of 74.4 % is achieved, provided that the AWF inputs are known, namely, wind farm thrust and power coefficients. The reduction in CPU hours is further reduced when all wind farms are represented by AWF models; namely 89.3 % and 99.9 %, for the double wind farm case and for a wind farm cluster case consisting of three wind farms, respectively. For the double wind farm case, the RANS models predict different wind speed flow fields compared to output from simulations performed with the mesoscale Weather Research and Forecasting model (WRF), but the models are in agreement with the inflow wind speed of the downstream wind farm. The double wind farm case is also simulated with the TurbOPark engineering wake model. Similar wake shapes are reproduced by TurbOPark but the model predicts a larger wind farm wake magnitude compared to RANS and WRF. TurbOPark predicts much better results when its ground model is switched off and a wake expansion coefficient of 0.06 is used. The RANS-AD-AWF model is also validated with SCADA measurements in terms of wind farm shape; the model captures the trend of the measurements for a wide range of wind directions, although the SCADA measurements indicate more pronounced wind farm wake shapes for certain wind directions.

Background Oesophagogastric (OG) cancer resections are technically challenging and associated with peri-operative morbidity. Practice has evolved from open to minimally invasive surgery (MIS), with ERAS has seen peri-operative outcomes improve. OG surgeons have not transitioned to MIS at the rate of others; 2021 NOGCA results showed that 17.6% of oesophagectomies and 17% of gastrectomies were performed as MIS. Concerns regarding the technical ability to perform safe anastomoses and appropriate oncological clearance have been cited as common reasons for surgeons not transitioning to MIS. GSTT is a high-volume OG unit which has transitioned from a fully open to predominantly MIS practice. The unit has performed over 100 minimally invasive Ivor Lewis oesophagectomies and 97 laparoscopic gastrectomies, it was therefore decided to analyse the unit's peri-operative outcomes to ensure that appropriate standards were maintained during this change in practice. The primary aim of this study was to examine a decade of peri-operative outcomes for Ivor Lewis oesophagectomy and gastrectomies, comparing parallel open and MIS cohorts. The secondary aim is to perform a sequential cumulative sum control chart (CUSM) analysis of the cohort to determine whether a learning curve effect for OG MIS can be demonstrated. Methods A retrospective analysis of a prospectively maintained comprehensive local database was performed. The results were cross-checked with NOCGA data, and a notes review was performed to capture any missing data.All Ivor Lewis oesophagectomy and gastrectomy (total, extended total and subtotal) performed for adenocarcinoma, squamous cell carcinoma, neuroendocrine tumours and high grade dysplasia at Guy's and St Thomas’ NHS Foundation Trust, London, UK over a ten-year period (January 2012- December 2021) were included. MIS for oesophagectomy was defined as an Ivor Lewis oesophagectomy performed with both laparoscopic and thoracoscopic phases. A hybrid (laparoscopic abdomen and open chest phase) oesophagectomy was grouped with a two-phase open procedure to create an open cohort. Laparoscopic gastrectomy (with a laparoscopic oesophago-jejunostomy or gastro-jejunostomy for sub-total gastrectomy) was used as the definition of MIS. The cohorts were compared for: age, sex, BMI and use of neoadjuvant therapy. Temporal trends in surgical approaches were compared as were Individual surgeon (n=4) volumes. Peri-operative clinical and oncological outcomes including length of stay, anastomotic leak, return to theatre, chest complications, resection margins and lymph node harvest were all examined. A CUSM analysis is currently being completed to further analyse surgeon performance over time. Results 596 patients underwent resection in well matched cohorts, 197 patients had an oesophagectomy (100 MIO), 339 had a gastrectomy (97 laparoscopic). MIS rates increased with no operations being performed as MIS in 2012 compared to 81% of oesophagectomy and 67% of gastrectomy performed as MIS in 2021. Two surgeons performed over 170 resections with MIS rate over 40%. OR of MIS performed by a high-volume surgeon was 3.01 (p Anastomotic leak rates following gastrectomy were 2% in both groups (p=0.66), 9% following open oesophagectomy and 11% after MIO (p=0.77). 10% of laparoscopic gastrectomy patients experienced a chest complication, 26% after open surgery, 22% MIO and 24% open (p=0.65). Mean length of stay was significantly reduced after MIS. An R0 rate of 96% was seen after laparoscopic gastrectomy, 90% after open (p=0.08). 68% of MIO patients had R0 resection compared to 70% after open. Positive CRM was 29% after MIO. The mean lymph node harvest was 29 after laparoscopic gastrectomy and 26 after open (p=0.24), 29 following MIO, 30 after open oesophagectomy. 97% of MIO harvested over 15 nodes. Conclusions This study demonstrates that a transition from open to MIS practice is achievable in the UK. Outcomes demonstrated similar peri-operative clinical and oncological outcomes between MIS and open surgery which addresses the concerns that prohibited the widespread uptake of MIS in UK centres. Developing a reliable surgical technique for lymphadenectomy and anastomoses that transitioned from open to hybrid and now MIS allowed for appropriate outcomes to be maintained. Unit outcomes compare well to both NOGCA/ECCG data with complication rates following MIO being significantly lower when compared to ECCG. Lymph node harvests were significantly higher in unit MIOs when compared to NOGCA (p=0.01). Volume played an important role in surgeons performing independent MIS. This should be considered when planning unit workload or a transition to MIS. It will be further explored in the CUSM analysis. A positive CRM was seen in more cases (29%) when compared to NOGCA (24%) and may be related to the preferred neoadjuvant regime being chemotherapy over chemoradiotherapy. The future of OG is moving towards robotic surgery. It is proposed that the evolution from open to MIS will make a second transition to robotics less challenging as the strategies needed to perform MIS have been addressed.

Background 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is routinely used for staging of oesophageal cancer and has an emerging role in assessing response to neoadjuvant therapy. Several studies have demonstrated that a reduction in FDG avidity of the primary tumour and loco-regional lymph nodes following neoadjuvant chemotherapy predicts pathological response and survival in this patient group. However, no studies have evaluated the prognostic significance of metabolic parameters with respect to pathological response in lymph nodes. Change in primary tumour maximum standardised uptake value (SUVmax) is the most widely used FDG PET-CT parameter to define metabolic response, with various thresholds described. The most commonly utilised are a 35% reduction in SUVmax (MUNICON), and a 30% reduction in SUVmax (PERCIST). However, there is no consensus regarding the optimal classification; the MUNICON threshold was derived from only 40 patients and PERCIST is not tumour specific. The primary aim of this study was to evaluate the ability of FDG PET-CT to predict pathological response in the primary tumour (pTR) and lymph nodes (pNR) in patients with oesophageal adenocarcinoma undergoing neoadjuvant chemotherapy before surgery. Secondary aims were to assess the prognostic effect of metabolic and pathological response and evaluate the predictive ability of response classifications. Methods Cohort study of 75 patients with locally advanced oesophageal or oesophago-gastric junctional adenocarcinoma who underwent FDG-PET-CT before and after neoadjuvant chemotherapy, prior to surgical resection at Guy's and St Thomas’ NHS Foundation Trust, London, UK, between 2017–2020. SUV metrics related to the primary tumour and loco-regional lymph nodes were derived on pre- and post- treatment FDG PET-CT. pTR and pNR were evaluated using the Mandard classification. Patients with Mandard scores of 1–3 were classified as pathological responders and those with Mandard scores of 4–5 as non-responders. Clinicopathological characteristics were compared using the Chi-squared test. Receiver operator characteristic (ROC) analysis was performed and area under the curve (AUC) calculated to determine optimum SUVmax thresholds for metabolic response in the primary tumour (mTR) and lymph nodes (mNR). Survival curves were created using the Kaplan-Meier method, with subgroups compared using the log-rank test. Survival analysis was performed using Cox proportional hazards regression providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age (continuous), sex (male or female), chemotherapy regimen (ECX or FLOT), cT stage (cT1–2 or cT3–4), cN stage (cN0 or cN+), tumour grade (well / moderately differentiated or poorly differentiated) and presence of signet ring cells (yes or no). Results Mean age was 63 years with the majority male (86.7%). Almost two thirds received FLOT (48/75, 64.0%) with the remainder receiving ECX chemotherapy. There was discordance between pathological response in the primary tumour and lymph nodes in several patients, including 23.1% (6/26) who demonstrated a lymph node response in the absence of a response in the primary tumour. ROC analysis demonstrated an optimum tumour SUVmax decrease of 51.2% for predicting pTR. Using a pragmatic cut-off of 50% this provided better prediction of pTR (AUC 0.714, sensitivity 73.5%, specificity 69.2%, p Conclusions In this study metabolic response on FDG PET-CT after neoadjuvant chemotherapy was predictive of pathological response in both the primary tumour and lymph node metastases of patients with oesophageal adenocarcinoma. Patients who had a favourable metabolic or pathological response in the primary tumour or lymph nodes had improved survival compared to non-responders. It has been suggested that commonly utilised thresholds of SUVmax are not optimal for response assessment in this patient group. This is supported by the results of the present study which suggest a reduction in SUVmax of 50% in the primary tumour was not only a better predictor of pathologic response, but also tumour recurrence and survival compared with PERCIST and MUNICON criteria. No previous studies have evaluated the ability of FDG PET-CT to predict pathologic nodal response despite recent findings suggesting it is an independent predictor of survival and evidence of a discrepancy, in some patients, who demostrate a nodal response in the absence of a response in the primary tumour. The use of FDG PET-CT in assessing response to neoadjuvant chemotherapy remains an under researched area and further evaluation is needed to establish whether it could be used to tailor individualised treatment strategies.

Background Type I gastric neuroendocrine neoplasms (g-NENs) have a low risk of metastasis and a generally favourable prognosis. Patients with small type I g-NENs (≤10mm) frequently require no treatment, whereas those with larger polyps usually undergo resection. We evaluated the safety and outcomes of endoscopic surveillance after no initial treatment in selected patients with type I g-NENs. Methods Retrospective analysis of type I g-NEN patients across two European Neuroendocrine Tumour Society Centers of Excellence 2003–2019. Results Following initial assessment, 87 of 115 patients with type I g-NEN (75 with polyps ≤10mm) received no initial treatment and underwent endoscopic surveillance. 79/87 (91%) demonstrated no clinically meaningful change in tumour size or grade over a median 62 month follow up. Only two patients developed NEN progression that required a change in management and two other patients developed gastric adenocarcinoma/high grade dysplasia; all four initially had ≥11mm g-NENs. Conclusions Patients with ≤10mm type I g-NENs were unlikely to develop clinically significant tumour progression and in most cases, resection was not needed. The endoscopic surveillance interval could therefore potentially be safely increased to every 2–3 years in such patients. However, lifelong surveillance is still advocated due to the additional risk of developing gastric adenocarcinoma.

Background The prognostic benefits of primary tumour and lymph node (LN) downstaging after neoadjuvant chemotherapy for oesophageal adenocarcinoma are well described. Pathological primary tumour regression grading (TRG) is widely used in the assessment of response to chemotherapy and has been shown to have prognostic value in this patient group. However, there is a lack of robust evidence regarding the prognostic effect of pathological response in LN despite emerging evidence of a discrepancy, up to 25% of patients in some studies, between TRG in the primary tumour and response in regional LNs. Although primary tumour regression is routinely documented as part of the standard pathological reporting of oesophagectomy specimens, LN regression is generally overlooked despite it's potential prognostic value. The aim of this study was to investigate the relationship between pathological response in LN, tumour recurrence and survival. Methods Multicentre cohort study including 763 patients with oesophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgery at Guy's and St Thomas’ NHS Foundation Trust (NHS-FT), The Royal Marsden NHS-FT, University Hospitals Birmingham NHS-FT, University Hospital Southampton NHS-FT and Belfast Health and Social Care Trust. Tumour regression was assessed in the primary tumour (as described by Mandard) and, retrospectively, in LNs retrieved from oesophagectomy specimens. LN were graded according to the proportion of fibrosis and residual tumour providing a LN regression score (LNRS). LNRS 1, complete response; LNRS 2, < 10% remaining tumour; LNRS 3, 10–50% remaining tumour; LNRS 4, > 50% viable tumour; LNRS 5, no evidence of response. Regression was defined as a LNRS of 1–3. Patients were classified as LN negative (no evidence of tumour or regression in any LN), complete LN-responders (evidence of regression ≥1 LN, no residual tumour in any LN), partial LN-responders (evidence of regression ≥1 LN with residual tumour ≥1 LN) and LN non-responders (no or minimal regression in any LN). Survival analysis was performed using multivariable Cox regression providing hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, gender, chemotherapy regimen, clinical stage, tumour grade, lympho-vascular invasion and primary tumour response. Results Mean age was 63 years with the majority male (86.2%). In total, 17,930 LN from 763 patients were analysed for evidence of response to chemotherapy. Overall, 243 (31.8%) patients were classified as LN negative, 62 (8.1%) as complete LN-responders, 155 (20.3%) as partial LN-responders and 303 (39.7%) as LN non-responders. Less than half (322/763, 42.2%) of patients demonstrated a pathological response in the primary tumour (Mandard score 1–3). Some patients had a LN response in the absence of a response in the primary tumour (97/431, 22.5%). Multivariable Cox regression survival analysis demonstrated improved overall survival in complete LN-responders (HR 0.37 95% CI 0.24–0.58), partial LN-responders (HR 0.70 95% CI 0.55–0.89) and LN negative patients (HR 0.34 95% CI 0.26–0.44) compared to LN non-responders. Similar results were observed for disease-free survival (complete LN-responders, HR 0.34 95% CI 0.22–0.53; partial LN-responders, HR 0.74 95% CI 0.58–0.93; LN negative, HR 0.33 95% CI 0.25–0.42). Rates of tumour recurrence were lower in patients who demonstrated a LN response or had negative LN (LN negative 23.0% vs complete LN-responders 19.4% vs partial LN-responders 50.3% vs LN non-responders 66.7%, p Conclusions In this cohort of patients with oeosphageal adenocarcinoma treated with neoadjuvant chemotherapy prior to surgical resection, LN regression was a strong predictive factor for better survival. This relationship was independent of primary tumour response, which was discordant in a significant number of patients. Complete LN-responders had equivalent survival to those with negative LN. Complete and partial LN-responders had better survival than LN non-responders. Evaluation and documentation of LN regression should be considered during the standard pathological reporting of oesophagectomy specimens.

Background In the era of evidence-based practice, there remains significant variation in peri-operative nutritional strategies for patients undergoing oesophagogastric (OG) cancer resections. Although dietary support is accepted as essential for this patient group, the use of feeding adjuncts, such as parenteral nutrition (PN) or enteral feeding tubes, varies widely. In addition, the clinical benefit of peri-operative supplementary feeding remains uncertain, especially since the evolution to minimally invasive OG surgery, introduction of ERAS and drive for early oral intake. Despite improvements in peri-operative nutrition pathways, risks associated with feeding adjuncts remain. There are also increased financial costs associated with peri-operative nutritional support which require consideration. After analysing unit peri-operative outcomes, it was hypothesised that routine feeding adjunct use may be unnecessary for most patients who meet oral nutritional goals early and should instead be reserved for patients with an increased risk of supplementary post-operative nutritional requirement.The primary aim of this study was to evaluate which clinicopathological factors were associated with prolonged use of PN after OG surgery. The secondary aim was to evaluate the associated morbidity and healthcare costs of PN use. Methods A retrospective cohort study of 518 patients undergoing oesophagectomy or total gastrectomy for cancer at Guy's and St Thomas’ NHS Foundation Trust, London, UK, between 2015 and 2021. The standard feeding regimen after oeosphagectomy or total gastrectomy at St Thomas’ involves PN for a median of eight days post-operatively. Oral intake is initiated after a contrast swallow is performed on day three for uncomplicated patients. The primary outcome was prolonged use of post-operative PN, defined as nine-days or more PN during the index admission. Clinicopathological characteristics were compared using the Chi square test. The relationship between these characteristics and PN use was evaluated using logistic regression analysis, providing odds ratios (OR) with 95% confidence intervals (CI) adjusting for age, sex, BMI, comorbidities, histology, anastomosis location, surgical access, pre-operative weight loss, pre-operative supplementary feeding. The prognostic ability of clinicopathological characteristics to predict prolonged PN use were compared using receiver operator characteristic (ROC) analysis to calculate area under the curve (AUC). An economic model was developed using described PN related complication rates from the published literature and 2021 NHS tariffs. Results Predictive factors for prolonged PN use on adjusted analysis included age over 65 (HR 1.70 95% CI 1.14–2.52), pre-operative weight loss (0–10%: HR 1.67 95% CI 1.09–2.56, >10%: HR 2.21 95% CI 1.05–4.66), open surgery (HR 1.64 95% CI 1.03–2.62) and an OG anastomosis located in the neck (HR 2.50 95% CI 1.35–4.65). Patients with a BMI over 25 had a lower chance of prolonged PN use (HR 0.65 95% CI 0.43–0.98). Other characteristics were not prognostic. ROC curve analysis demonstrated that anastomosis location (AUC 0.59), age (AUC 0.57) and surgical access (AUC 0.56) were the most prognostic factors. The combination of parameters included in the adjusted model provided an AUC of 0.67. Potential PN and line related complications included: deranged liver biochemistry (18.0%), deranged blood sugars (9%), line infection (1.4%) and line thrombus (0.8%). An eight-day course of PN was calculated to cost £884 with average treatment related complication costs of £176 per patient. Using the mean number of patients treated per year over the past three years (N = 112) the projected service savings were £75,912 per year if PN was reserved for patients with high-risk characteristics. Conclusions This study has demonstrated that several patient and treatment related factors are associated with an increased risk of needing prolonged adjunctive nutritional support after OG surgery. As surgical practice has evolved to minimally invasive surgery and ERAS with subsequently low peri-operative complication rates, the clinical benefits of short course adjuvant feeding may not be seen in patients who progress promptly to appropriate oral intake. Therefore, we propose the introduction of a tailored treatment pathway, based on pre-operative characteristics which excludes the routine use of post-operative feeding for low-risk patients. The study also demonstrates that a change in practice can lead to considerable cost savings. The model demonstrated in this study can be applied to all feeding adjuncts and can therefore be universally adopted in any UK/global unit regardless of supplementary feeding route preference. It will encourage high-performance by promoting a patient-centred and individualised approach to peri-operative nutrition which is currently lacking in many aspects of our clinical practice. Further work in the form of a randomised trial may be explored to better understand the need and benefit of supplementary feeding methods after OG resection as the specialty continues to evolve.

BACKGROUND Neoadjuvant chemotherapy is often used prior to surgical resection for oesophageal adenocarcinoma but remains ineffective in a high proportion of patients. The histological Mandard tumour regression grade is used to determine chemoresponse but is not available at the time of treatment decision-making. The aim of this cohort study was to identify factors that predict chemotherapy response prior to surgery. METHODS A prospectively collected database of patients undergoing surgical resection for oesophageal adenocarcinoma from a high-volume UK institution was used. Patients were subcategorised using pathological tumour response into 'responders' (Mandard grade 1-3) and 'non-responders' (Mandard grade 4 and 5). Multivariable logistic regression analysis was performed to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for responder status adjusting for a variety of parameters. Receiver operating characteristic (ROC) curves were calculated. RESULTS Among 315 patients included, 102 (32%) were responders and 213 (68%) non-responders. A decrease in radiological tumour volume (OR 1.92 95%CI 1.02-3.62; p = 0.05), a 'partial response' RECIST score (OR 7.16 95%CI 1.49-34.36; p = 0.01), a clinically improved dysphagia score (OR 2.79 95%CI 1.05-7.04; p = 0.04) and lymphovascular invasion (OR 0.06 95%CI 0.02-0.13; p = 0.000) influenced responder status. ROC curve analysis for responder status utilising all available parameters had an area under the curve (AUC) of 0.86. CONCLUSION This study has highlighted the potential for using pre-defined factors to identify those patients who have responded to neoadjuvant chemotherapy, prior to surgical resection, potentially facilitating a more individualised therapeutic approach.

The prognostic benefit of primary tumour and lymph node (LN) downstaging after neoadjuvant chemotherapy for oesophageal adenocarcinoma (OAC) is well described. However, there is no robust evidence regarding the prognostic effect of pathological LN regression despite emerging evidence of a discrepancy, in some patients, between tumour regression grade in the primary tumour and response in regional LNs. The aim of this study was to investigate the relationship between pathological LN regression, tumour recurrence and survival. Retrospective, multicentre cohort study including 763 patients with OAC treated with neoadjuvant chemotherapy followed by surgery at 5 high-volume tertiary referral centres in the United Kingdom. Tumour regression was assessed in the primary tumour (Mandard) and LNs retrieved from oesophagectomy specimens. Patients were classified as LN negative (no evidence of tumour or regression in any LN), complete LN-responders (evidence of regression ≥1 LN, no residual tumour in any LN), partial LN-responders (evidence of regression ≥1 LN with residual tumour ≥1 LN) and LN non-responders (no or minimal regression in any LN). Survival analysis was performed using Kaplan-Meier and Cox regression. Overall, 243 (31.8%) patients were classified as LN negative, 62 (8.1%) as complete LN-responders, 155 (20.3%) as partial LN-responders and 303 (39.7%) as LN non-responders. Some patients had a LN response in the absence of a response in the primary tumour (97/431, 22.5%). Multivariable Cox regression survival analysis (adjusting for age, gender, chemotherapy regimen, clinical stage, tumour grade, lympho-vascular invasion and primary tumour response) demonstrated improved overall survival in complete LN-responders (Hazard ratio (HR) 0.37 95% confidence interval (CI) 0.24-0.58), partial LN-responders (HR 0.70 95% CI 0.55-0.89) and LN negative patients (HR 0.34 95% CI 0.26-0.44) compared to LN non-responders. In this cohort of patients with OAC treated with neoadjuvant chemotherapy prior to surgical resection, LN regression was a strong prognostic factor independent of primary tumour response, which was discordant in a significant number of patients. Complete LN-responders had equivalent survival to those with negative LN. Complete and partial LN-responders had better survival than LN non-responders. Evaluation and documentation of LN regression should be considered during the standard pathological reporting of oesophagectomy specimens.

2-deoxy-2[18F]fluoro-D-glucose positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging of oesophageal cancer and has an emerging role in assessing response to neoadjuvant therapy. The primary aim of this study was to evaluate the ability of FDG-PET-CT to predict pathological response in the primary tumour (pTR) and lymph nodes (pNR) in patients with oesophageal adenocarcinoma undergoing neoadjuvant chemotherapy before surgery. The secondary aim was to assess the prognostic effect of metabolic and pathological response. Cohort study of 75 patients with locally advanced oesophageal or oesophago-gastric junctional adenocarcinoma who underwent FDG-PET-CT before and after neo-adjuvant chemotherapy, prior to surgical resection at a tertiary referral centre in the United Kingdom, between 2017-2020. Standardised uptake value (SUV) metrics related to the primary tumour and loco-regional lymph nodes were derived. pTR and pNR were evaluated using the Mandard classification. Receiver operator characteristic (ROC) analysis was performed and area under the curve (AUC) calculated to determine optimum SUVmax thresholds for metabolic response in the primary tumour (mTR) and lymph nodes (mNR). Survival was assessed using multivariable Cox regression. ROC analysis demonstrated an optimum tumour SUVmax decrease of 51.2% for predicting pTR. A pragmatic 50% cut-off provided better prediction of pTR (AUC 0.714, sensitivity 73.5%, specificity 69.2%, p Metabolic response predicted pathological response in both the primary tumour and lymph nodes in this cohort of patients with locally advanced oesophageal adenocarcinoma treated with neo-adjuvant chemotherapy. Metabolic tumour response, pathological tumour response, metabolic nodal response and pathological nodal response were all independent prognostic factors for survival. Currently utilised metabolic response criteria may not be optimal for this tumour group.

The clinical value of multiple staging investigations for high-grade dysplasia (HGD) or early adenocarcinoma of the oesophagus (EOC) is unclear. A single centre prospective cohort of patients treated for EOC between 2000 and 2019 was analysed. This coincided with a transition period from oesophagectomy to endoscopic mucosal resection (EMR) as the treatment of choice for early cancers. All patients were staged with computed tomography (CT), endoscopic ultrasound (EUS), and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)-CT. The aim of this study was to assess the accuracy of these investigations and impact on clinical management. 297 patients with HGD or EOC were included (EMRn = 184; oesophagectomy n = 113 [preceded by EMRn = 23]). Staging patterns for both groups were similar throughout staging modalities (CT, EUS, PET-CT), showing low overall accuracy. In the EMR group, over-staging that might have changed management occurred in 10 patients (3.6%)for T-staging (T2) and 14 patients (5.0%)for positive lymph node-staging (LNM). In the oesophagectomy alone group LNM identified following surgery was rare (8.9%) and staging sensitivity for these surgically treated patients was low (CT 12.5%, EUS 12.5%, PET-CT 0.0%). Overall, PET-CT and EUS changed decision-making in less than 1%of patients with a clear CT and low risk histology criteria on EMR specimen. Staging accuracy is low in EOC and the addition of EUS and PET-CT does not change patient decision making significantly. Histology obtained from EMR specimens contain important predicting factors that do change patient management, proving to be an excellent staging tool rather than imaging techniques, hence, EUS and PET-CT should only be used selectively in patients being assessed for EOC.

BACKGROUND Most patients presenting with oesophageal cancer do so with advanced disease not suitable for surgery. However, there are examples of encouraging survival following surgery in highly selected patients who respond well to chemotherapy. METHODS This was a retrospective cohort study of patients who presented with advanced but nonvisceral metastatic oesophageal cancer. Consecutive patients on a prolonged primary chemotherapy pathway who underwent surgical resection following a favourable response to chemotherapy were included. Survival and recurrence rates were analysed using Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS A total of 57 patients included in the cohort operated between 2007 and 2015, the overall median survival was 44 months and the 5-year survival was 42%. Prechemotherapy cN0/cN1 (HR: 0.27, 95% CI: 0.12-0.62) conferred an independent survival advantage compared to cN2 and cN3 disease. Poor differentiation (HR: 2.46, 95% CI: 1.11-5.42), R1 resection (HR: 2.43, 95% CI: 1.14-5.19) and advanced nodal status (HR: 3.28, 95% CI: 1.44-7.47) predicted worse survival on univariable analysis. Poor differentiation (HR: 3.93, 95% CI: 1.62-9.56) was independently associated with poor survival when adjusted for other variables. CONCLUSION Patients who present with advanced inoperable oesophageal cancer who have a favourable response to chemotherapy represent a limited group of patients who may benefit from surgery.

This paper uses a two-sector open economy model to examine the dynamic absorption of foreign aid in the presence of both formal and informal production. Calibrating the model to yield a long-run equilibrium consistent with sample averages for 72 aid-recipient developing countries for the period 1990-2017, we show that an increase in foreign aid impacts the sectoral composition of the recipient economy, driving resources into the informal sector, and away from the formal sector. Further, if aid is untied (say, provided for general budget support), then the expansion of the informal sector can lead to a contraction of the aggregate economy through the Dutch Disease effect. If the recipient government’s objective is to drive an economic expansion by increasing the share of formal production, then re-allocating existing aid to public investment is more effective than an increase in the aggregate level of aid.