Patient-reported outcomes after oesophagectomy in the multicentre LASER study.

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Nosocomial SARS-CoV-2 transmission in postoperative infection and mortality: analysis of 14 798 procedures.

This study used a national administrative database to estimate perioperative SARS-CoV-2 infection risk, and associated mortality, relative to nosocomial transmission rates. The impact of nosocomial transmission was greatest after major emergency surgery, whereas laparoscopic surgery may be protective owing to reduced duration of hospital stay. Procedure-specific risk estimates are provided to facilitate surgical decision-making and informed consent. Estimated risks.

3D characterisation of dry powder inhaler formulations: Developing X-ray micro computed tomography approaches.

Carrier-based dry powder inhaler (DPI) formulations need to be accurately characterised for their particle size distributions, surface roughnesses, fines contents and flow properties. Understanding the micro-structure of the powder formulation is crucial, yet current characterisation methods give incomplete information. Commonly used techniques like laser diffraction (LD) and optical microscopy (OM) are limited due to the assumption of sphericity and can give variable results depending on particle orientation and dispersion. The aim of this work was to develop new three dimensional (3D) powder analytical techniques using X-ray computed tomography (XCT) that could be employed for non-destructive metrology of inhaled formulations. α-lactose monohydrate powders with different characteristics have been analysed, and their size and shape (sphericity/aspect ratio) distributions compared with results from LD and OM. The three techniques were shown to produce comparable size distributions, while the different shape distributions from XCT and OM highlight the difference between 2D and 3D imaging. The effect of micro-structure on flowability was also analysed through 3D measurements of void volume and tap density. This study has demonstrated for the first time that XCT provides an invaluable, non-destructive and analytical approach to obtain number- and volume-based particle size distributions of DPI formulations in 3D space, and for unique 3D characterisation of powder micro-structure.

Red light at night permits the nocturnal rise of melatonin production in horses.

Exposure to white light at night suppresses melatonin production, impacts circadian rhythms and contributes to ill-health in humans. Human interaction with horses frequently occurs at night. We tested the hypothesis that dim red light would not suppress the nightly rise in serum melatonin levels in horses. In a crossover design, six horses were maintained for consecutive 48h periods under a Light: Red (LR) and a Light: Dark (LD) photo-schedule. Transitions from light (>200lux, polychromatic white light) to red (5lux, peak wavelength 625nm) or dark (<0.5lux), and vice versa, coincided with ambient sunset and sunrise times. Blood was collected at 2h intervals for 24h during each treatment via indwelling jugular catheters. Samples were harvested for serum and stored at -20°C until assayed for melatonin by radioimmunoassay. Repeated measures two-way ANOVA and t-tests analysed for differences in LR and LD melatonin profiles and their circadian rhythm parameters. No time×treatment interaction or effect of treatment on serum melatonin levels were demonstrated (P>0.05). A robust main effect of time (P<0.0001) predominated, with melatonin levels rising at night under both treatments. Statistically significant differences were not observed when LR and LD were compared for circadian rhythm measures of night time peak, area under the curve (AUC), or for times of onset (evening rise), offset (morning decline), or peak duration. Low intensity red light at night did not impact the pattern of melatonin secretion in this study and is, therefore, unlikely to impact the physiology of circadian or seasonal regulation.

Measuring the impact of oesophagectomy on physical functioning and physical activity participation: a prospective study.

BACKGROUND: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. METHODS: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. RESULTS: Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p < 0.001). Percentage time spent sedentary increased throughout recovery (p < 0.001) and remained significantly higher at T2 in comparison to T0 (p = 0.003). In contrast, percentage time spent engaged in either light or moderate-to-vigorous intensity activity, all reduced significantly (p < 0.001 for both) and remained significantly lower at T2 in comparison to T0 (p = 0.009 and p = 0.01 respectively). Patients reported deficits in multiple domains of HR-QOL during recovery including global health status (p = 0.04), physical functioning (p < 0.001) and role functioning (p < 0.001). Role functioning remained a clinically important 33-points lower than pre-operative values at T2. CONCLUSION: Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy. Physical activity is a measurable and modifiable target for physical rehabilitation, which is closely aligned with patient-reported deficits in role functioning. Rehabilitation aimed at optimising physical health in oesophageal cancer survivorship is warranted.

Effect of neoadjuvant chemoradiation on preoperative pulmonary physiology, postoperative respiratory complications and quality of life in patients with oesophageal cancer.

BACKGROUND: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer. METHODS: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose-volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41·4 Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1 month after nCRT. Radiation-induced lung injury (grade 2 or greater), comprehensive complications index (CCI) and pulmonary complications were monitored prospectively. Health-related quality of life was assessed among disease-free patients in survivorship. RESULTS: Some 228 patients were studied. Comparing pulmonary physiology values before with those after nCRT, FEV1 decreased from mean(s.d.) 96·8(17·7) to 91·5(20·4) per cent (-3·6(10·6) per cent; P < 0·001), FVC from 104·9(15·6) to 98·1(19·8) per cent (-3·2(11·9) per cent; P = 0·005) and DLCO from 97·6(20·7) to 82·2(20·4) per cent (-14·8(14·0) per cent; P < 0·001). Five patients (2·2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P = 0·005) and increased age (P < 0·001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41·4 Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40 Gy (P = 0·001). On multivariable analysis, post-treatment DLCO predicted CCI (P = 0·006), respiratory failure (P = 0·020) and reduced physical function in survivorship (P = 0·047). CONCLUSION: These data indicate that modern nCRT alters pulmonary physiology, in particular diffusion capacity, which is linked to short- and longer-term clinical consequences, highlighting a potentially modifiable index of risk.

ANTECEDENTES: El tema de si en el cáncer de esófago la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiation, nCRT) repercute sobre la morbilidad postoperatoria, especialmente sobre la morbilidad pulmonar y la calidad de vida de los pacientes que sobreviven sigue siendo controvertido. Este estudio combina datos sobre resultados clínicos con una evaluación sistemática de la fisiología pulmonar para determinar el impacto de la nCRT sobre la fisiología pulmonar y los resultados clínicos en el cáncer de esófago localmente avanzado. MÉTODOS: Se incluyeron pacientes consecutivos tratados entre 2010-2016. La radioterapia conformal 3D fue la estándar, con un histograma dosis-volumen del pulmón V20 < 25% y radiación entre 40-41,4 Gy. Se evaluaron el volumen espiratorio forzado (forced expiratory volume, FEV1), la capacidad vital forzada (forced vital capacity, FVC) y la capacidad de difusión del monóxido de carbono (diffusion capacity for carbon monoxide, DLCO) al inicio y un mes tras la nCRT. La lesión pulmonar inducida por la radioterapia (EORTC grado ≥ 2), el índice de complicaciones integral (comprehensive complications index, CCI), grado de Clavien-Dindo, y complicaciones pulmonares fueron analizadas de manera prospectiva. Se evaluó la calidad de vida relacionada con la salud entre los pacientes supervivientes libres de enfermedad (EORTC QLQ-C30, OG25, OES18). RESULTADOS: Se estudiaron un total de 228 pacientes. Al comparar los valores de la fisiología pulmonar antes y después de la nCRT respectivamente, la FEV1 disminuyó de 96,8 ± 17,7% a 91,5 ± 20,4% (-3,6 ± 10,6%, P = 0,0002), la FVC de 104,9 ± 15,6 a 98,1 ± 19,8% (-3,2 ± 11,9%, P = 0,005) y la DLCO de 97,6 ± 20,7 a 82,2 ± 20,4% (-14,8 ± 14,0%, P < 0,0001). Cinco pacientes (2,2%) desarrollaron lesión pulmonar relacionada con la radioterapia impidiendo la resección quirúrgica. Los factores predictores independientes de %ΔDLCO fueron el hábito tabáquico (P = 0,005) y la edad avanzada (P < 0,001). El tratamiento con carboplatino/paclitaxel/41,4Gy determinó un mayor descenso de la DLCO en comparación con cisplatino/5-fluorouracilo/40Gy (P = 0,001). En el análisis multivariable, la DLCO tras el tratamiento fue una variable predictora de CCI (P = 0,006), fracaso respiratorio/intubación prolongada (P = 0,020) y reducción de la función física en los supervivientes (P = 0,047). CONCLUSIÓN: Estos datos indican que la moderna nCRT altera la fisiología pulmonar, especialmente la difusión pulmonar, con consecuencias clínicas a corto y largo plazo. La DLCO podría constituir un factor de riesgo potencialmente modificable.

Cardiorespiratory Comorbidity and Postoperative Complications following Esophagectomy: a European Multicenter Cohort Study.

BACKGROUND: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. PATIENTS AND METHODS: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. RESULTS: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien-Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11-3.04], pneumonia (OR 1.65, 95% CI 1.10-2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04-2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien-Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. CONCLUSIONS: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. METHODS: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

Optimizing land management strategies for maximum improvements in lake dissolved oxygen concentrations.

Eutrophication and anoxia are unresolved issues in many large waterbodies. Globally, management success has been inconsistent, highlighting the need to identify approaches which reliably improve water quality. We used a process-based model chain to quantify effectiveness of terrestrial nutrient control measures on in-lake nitrogen, phosphorus, chlorophyll and dissolved oxygen (DO) concentrations in Lake Simcoe, Canada. Across a baseline period of 2010-2016 hydrochemical outputs from catchment models INCA-N and INCA-P were used to drive the lake model PROTECH, which simulated water quality in the three main basins of the lake. Five terrestrial nutrient control strategies were evaluated. Effectiveness differed between catchments, and water quality responses to nutrient load reductions varied between deep and shallow lake basins. Nutrient load reductions were a significant driver of increased DO concentrations, however strategies which reduced tributary inflow had a greater impact on lake restoration, associated with changes in water temperature and chemistry. Importantly, when multiple strategies were implemented simultaneously, resultant large flow reductions induced warming throughout the water column. Negative impacts of lake warming on DO overwhelmed the positive effects of nutrient reduction, and limited the effectiveness of lake restoration strategies. This study indicates that rates of lake recovery may be accelerated through a coordinated management approach, which considers strategy interactions, and the potential for temperature change-induced physical and biological feedbacks. Identified impacts of flow and temperature on rates of lake recovery have implications for management sustainability under a changing climate.

Chromosomal fusion and life history-associated genomic variation contribute to within-river local adaptation of Atlantic salmon.

Chromosomal inversions have been implicated in facilitating adaptation in the face of high levels of gene flow, but whether chromosomal fusions also have similar potential remains poorly understood. Atlantic salmon are usually characterized by population structure at multiple spatial scales; however, this is not the case for tributaries of the Miramichi River in North America. To resolve genetic relationships between populations in this system and the potential for known chromosomal fusions to contribute to adaptation, we genotyped 728 juvenile salmon using a 50 K SNP array. Consistent with previous work, we report extremely weak overall population structuring (Global FST  = 0.004) and failed to support hierarchical structure between the river's two main branches. We provide the first genomic characterization of a previously described polymorphic fusion between chromosomes 8 and 29. Fusion genomic characteristics included high LD, reduced heterozygosity in the fused homokaryotes, and strong divergence between the fused and the unfused rearrangement. Population structure based on fusion karyotype was five times stronger than neutral variation (FST  = 0.019), and the frequency of the fusion was associated with summer precipitation supporting a hypothesis that this rearrangement may contribute local adaptation despite weak neutral differentiation. Additionally, both outlier variation among populations and a polygenic framework for characterizing adaptive variation in relation to climate identified a 250-Kb region of chromosome 9, including the gene six6 that has previously been linked to age-at-maturity and run-timing for this species. Overall, our results indicate that adaptive processes, independent of major river branching, are more important than neutral processes for structuring these populations.

Bridging the gap between terrestrial, riverine and limnological research: Application of a model chain to a mesotrophic lake in North America.

Models remain our best available tool for managing low lake dissolved oxygen concentrations, which pose a serious ecological risk. This study investigated whether process-based catchment models (INCA-N and INCA-P) could accurately drive a lake model (PROTECH), to bridge a gap between terrestrial, riverine and limnological research. INCA was calibrated over all 20 catchments of the Simcoe watershed, Canada. Daily outputs (flow, nitrogen and phosphorus concentrations) over the period 2010-2016 were selected for a common "baseline" period, and used as inputs to PROTECH, which was calibrated across the three major basins of lake Simcoe; Kempenfelt (K42), Cooks (C9), and the main basin (E51). Results showed that at catchment outflows INCA models achieved an average flow R2 of 0.8; a load R2 of 0.7 (both for TP and N-NO3), a concentration R2 of 0.4 and 0.5 (for TP and N-NO3 respectively), and an SiO2 R2>0.8. In each basin PROTECH achieved an R2 for both temperature and dissolved oxygen (DO) concentrations of >0.9. Performance of N-NO3, TP and Chlorophyll-a concentrations were good (R2 values of up to 0.98, 0.92 and 0.53 respectively). Multi-stressor analyses established that most occurrences when DO dropped below the desired 7mg/l threshold (DO7) were attributable to combinations of high temperatures and low tributary inflows. The importance of additional drivers was depth dependent, with photosynthesis being particularly important in shallower C9 and E51 basins during summer, when algae contributed sufficient O2 to the water column to inhibit DO7 events. Conversely in the deeper more strongly stratified K42 basin, greater algal growth boosted the biochemical oxygen demand, enhancing declines in DO. Lake physics explained a significant number of DO7 events in all three basins. Integrated catchment-lake modelling approaches are important in understanding lake physical and ecological processes, and the impacts of land management and future climate change.

Combined impacts of future land-use and climate stressors on water resources and quality in groundwater and surface waterbodies of the upper Thames river basin, UK.

It is widely acknowledged that waterbodies are becoming increasingly affected by a wide range of drivers of change arising from human activity. To illustrate how this can be quantified a linked modelling approach was applied in the Thames river basin in southern UK. Changes to river flows, water temperature, river and reservoir quality were predicted under three contrasting future "storylines"; one an extension of present day rates of economic development, the others representing more extreme and less sustainable visions. Modelling revealed that lower baseflow conditions will arise under all storylines. For the less extreme storyline river water quality is likely to deteriorate but reservoir quality will improve slightly. The two more extreme futures could not be supported by current management strategies to meet water demand. To satisfy these scenarios, transfer of river water from outside the Thames river basin would be necessary. Consequently, some improvement over present day water quality in the river may be seen, and for most indicators conditions would be better than in the less extreme storyline. However, because phosphorus concentrations will rise, the invoked changes in water demand management would not be of a form suitable to prevent a marked deterioration in reservoir water quality.

Gender differences for growth in North American Atlantic salmon.

An assumption in aquaculture of Atlantic salmon is that male and female growth within families is perfectly genetically correlated. That is, families would rank identically if based on male growth only or female growth only. Also, growth in freshwater and sea water is assumed to be highly correlated between males and females within families. However, structural analysis of the DNA of Atlantic salmon has found that the linkage maps of females differ significantly from that of males. Genetic variability for any trait measured on females could be greater or lesser than on males. Thus, male and female growth might be considered as separate traits giving rise to families ranking differently depending on gender. A multiple trait family model for weight and length at 3 years of age in Atlantic salmon according to gender was applied to data on North American Atlantic salmon obtained from the Oak Bay Hatchery in New Brunswick, Canada. Genetic correlations between male and female growth in both freshwater and sea water were estimated by Bayesian methods. The estimates support the possible existence of gender dimorphism in North American Atlantic salmon for growth traits.

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PURPOSE: Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. METHODS: Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). RESULTS: Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). CONCLUSIONS: Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Mesoscale simulations of confined Nafion thin films.

The morphology and transport properties of thin films of the ionomer Nafion, with thicknesses on the order of the bulk cluster size, have been investigated as a model system to explain the anomalous behaviour of catalyst/electrode-polymer interfaces in membrane electrode assemblies. We have employed dissipative particle dynamics (DPD) to investigate the interaction of water and fluorocarbon chains, with carbon and quartz as confining materials, for a wide range of operational water contents and film thicknesses. We found confinement-induced clustering of water perpendicular to the thin film. Hydrophobic carbon forms a water depletion zone near the film interface, whereas hydrophilic quartz results in a zone with excess water. There are, on average, oscillating water-rich and fluorocarbon-rich regions, in agreement with experimental results from neutron reflectometry. Water diffusivity shows increasing directional anisotropy of up to 30% with decreasing film thickness, depending on the hydrophilicity of the confining material. A percolation analysis revealed significant differences in water clustering and connectivity with the confining material. These findings indicate the fundamentally different nature of ionomer thin films, compared to membranes, and suggest explanations for increased ionic resistances observed in the catalyst layer.

A genome scan for selection signatures comparing farmed Atlantic salmon with two wild populations: Testing colocalization among outlier markers, candidate genes, and quantitative trait loci for production traits.

Comparative genome scans can be used to identify chromosome regions, but not traits, that are putatively under selection. Identification of targeted traits may be more likely in recently domesticated populations under strong artificial selection for increased production. We used a North American Atlantic salmon 6K SNP dataset to locate genome regions of an aquaculture strain (Saint John River) that were highly diverged from that of its putative wild founder population (Tobique River). First, admixed individuals with partial European ancestry were detected using STRUCTURE and removed from the dataset. Outlier loci were then identified as those showing extreme differentiation between the aquaculture population and the founder population. All Arlequin methods identified an overlapping subset of 17 outlier loci, three of which were also identified by BayeScan. Many outlier loci were near candidate genes and some were near published quantitative trait loci (QTLs) for growth, appetite, maturity, or disease resistance. Parallel comparisons using a wild, nonfounder population (Stewiacke River) yielded only one overlapping outlier locus as well as a known maturity QTL. We conclude that genome scans comparing a recently domesticated strain with its wild founder population can facilitate identification of candidate genes for traits known to have been under strong artificial selection.

Contact angles of surfactant solutions on heterogeneous surfaces.

Using Gibbs' adsorption equation and a literature isotherm, a new general model to predict the contact angle of surfactant solutions on (smooth or rough) chemically heterogeneous surfaces is constructed based on the Cassie equation. The model allows for adsorption at the liquid-vapor, solid-liquid, and solid-vapor interfaces. Solid-vapor adsorption is allowed in order to model the autophobic effect on hydrophilic surfaces. Using representative values for the coefficients which describe adsorption at each interface, model predictions for contact angles as a function of f parameters (area fractions) and surfactant concentration are made for heterogeneous surfaces made up of different materials. On smooth surfaces, the f parameters serve as weighting factors determining how to combine the effects of surfactant adsorption on each material to predict the behavior on the heterogeneous surface. Due to the non-linear nature of the model, the inclusion of a small amount of hydrophobic material has a greater effect on a predominantly hydrophilic material than vice versa, explaining the result seen in literature that a small amount of hydrophobic contamination (such as oil) significantly increases contact angle on a hydrophilic surface. The fact that even a small amount of heterogeneity can greatly change experimental results could lead to incorrect experimental conclusions about surfactant adsorption if a surface were wrongly assumed to be homogeneous. Model predictions rapidly become more complex as the number of differently wettable materials present on the surface increases. Also, an approximately equal weighting of different materials generally leads to more complex behaviors compared to heterogeneous surfaces composed largely of a single material. Rough heterogeneous surfaces follow previous results for surfactant wetting of rough homogeneous surfaces, leading to an amplification/attenuation of surfactant effects for penetrated/unpenetrated wetting, and further increasing the complexity of predictions. These potential complexities point to the importance of characterizing the heterogeneities of any surface under consideration. With proper characterization, the model described in this paper will allow for prediction of contact angles on all types of heterogeneous surfaces, and design of surfaces for specific interactions with surfactant solutions.